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      Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment

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          Abstract

          Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed ( p < 0.001), but not with episodic memory, semantic memory, working memory, or visuospatial abilities (all p > 0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed ( p = 0.013) and episodic memory ( p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume ( p < 0.001). In a model with both MRI-derived measures included, the relation of WMH to perceptual speed remained significant ( p < 0.001), while gray matter volumes were no longer related ( p = 0.14). This study of older community-dwelling individuals without overt cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.

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          Most cited references48

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          Overview and findings from the rush Memory and Aging Project.

          The Memory and Aging Project is a longitudinal, epidemiologic clinical-pathologic cohort study of common chronic conditions of aging with an emphasis on decline in cognitive and motor function and risk of Alzheimer's disease (AD). In this manuscript, we first summarize the study design and methods. Then, we present data on: (1) the relation of motor function to cognition, disability, and death; (2) the relation of risk factors to cognitive and motor outcomes, disability and death; (3) the relation of neuropathologic indices to cognitive outcomes; (4) the relation of risk factors to neuropathologic indices; and (5) additional study findings. The findings are discussed and contextualized.
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            Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study.

            Cerebral white matter lesions are a common finding on MRI in elderly persons. We studied the prevalence of white matter lesions and their relation with classic cardiovascular risk factors, thrombogenic factors, and cognitive function in an age- and gender-stratified random sample from the general population that consisted of 111 subjects 65 to 84 years of age. Overall, 27% of subjects had white matter lesions. The prevalence and severity of lesions increased with age. A history of stroke or myocardial infarction, factor VIIc activity, and fibrinogen level were each significantly and independently associated with the presence of white matter lesions. Significant relations with blood pressure level, hypertension, and plasma cholesterol were present only for subjects aged 65 to 74 years. White matter lesions tended to be associated with lower scores on tests of cognitive function and were significantly associated with subjective mental decline. This study suggests that classic cardiovascular risk factors, as well as thrombogenic factors, are associated with white matter lesions in subjects over 65 years of age in the general population, and that these lesions may be related to cognitive function.
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              The cognitive correlates of white matter abnormalities in normal aging: a quantitative review.

              Cerebral white matter of asymptomatic people frequently exhibits circumscribed areas of hyperintensity on magnetic resonance (MR) images and hypodensity on computed tomography scans. However, behavioral implications of this phenomenon remain unclear. In this meta-analysis, the authors examine cumulative evidence regarding the cognitive sequelae of white matter abnormalities in adults without dementia. The influence of potential moderator variables, such as neuroimaging technique, location of the lesions, rating scale, and demographic characteristics of the sample on the association between the burden of white matter hyperintensities and cognitive performance was also examined. Results indicate that white matter abnormalities observed on MR images are associated with attenuated performance on tasks of processing speed, immediate and delayed memory, executive functions, and indices of global cognitive functioning. There was no significant link between the white matter hyperintensities and psychometric indices of intelligence or fine motor performance.
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                Author and article information

                Contributors
                zarvanit@rush.edu
                Journal
                Brain Struct Funct
                Brain Struct Funct
                Brain Structure & Function
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1863-2653
                1863-2661
                2 April 2015
                2 April 2015
                2016
                : 221
                : 2135-2146
                Affiliations
                [ ]Rush Alzheimer’s Disease Center, Rush University Medical Center, 600 S. Paulina Ave, Suite 1020, Chicago, IL 60612 USA
                [ ]Department of Neurological Sciences, Rush University Medical Center, Chicago, USA
                [ ]Department of Behavioral Sciences, Rush University Medical Center, Chicago, USA
                [ ]Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, USA
                [ ]Department of Biomedical Engineering, Illinois Institute of Technology, Rush University Medical Center, Chicago, USA
                Article
                1034
                10.1007/s00429-015-1034-7
                4592368
                25833685
                7ec5fbf1-9766-4d1a-8943-71ce57687420
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                Categories
                Original Article
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2016

                Neurology
                aging,cognition,brain,mri,volume,white matter hyperintensities,gray matter,voxel-wise analyses
                Neurology
                aging, cognition, brain, mri, volume, white matter hyperintensities, gray matter, voxel-wise analyses

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