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      White matter hyperintensities, incident mild cognitive impairment, and cognitive decline in old age

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          Abstract

          Objective

          Examine the association of white matter hyperintensities ( WMH) with risk of incident mild cognitive impairment ( MCI) and rate of decline in multiple cognitive systems in community‐based older persons.

          Methods

          Participants ( n = 354) were older persons initially free of cognitive impairment from two ongoing longitudinal epidemiologic studies of aging. All underwent brain magnetic resonance imaging ( MRI) for quantification of WMH and gray matter volumes and detailed annual clinical evaluations including 17 cognitive tests. Proportional hazards models were used to examine the relationship between WMH and incident MCI, and mixed‐effects models were used to examine the relationship between WMH and decline in global cognition and five specific cognitive systems.

          Results

          During up to about 6 years of follow‐up (mean = 4.1), 106 (30% of 354) persons developed MCI. In a proportional hazards model adjusted for age, gender, and education, WMH volume was associated with a substantially increased risk of MCI ( P < 0.001). Thus, a person with a high WMH volume (90th percentile) was about 2.7 times more likely to develop MCI compared to a person with a low volume (10th percentile). WMH volume also was associated with an increased rate of decline in global cognition ( P < 0.001), perceptual speed, working memory, episodic memory, and semantic memory. Associations persisted after adjustment for total gray matter volume, vascular risk factors, and vascular diseases.

          Interpretation

          WMH contribute to the development of MCI and are associated with progressive decline in multiple cognitive systems in old age.

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          Most cited references15

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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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            Overview and findings from the religious orders study.

            The Religious Orders Study is a longitudinal clinical-pathologic cohort study of aging and Alzheimer's disease (AD). In this manuscript, we summarize the study methods including the study design and describe the clinical evaluation, assessment of risk factors, collection of ante-mortem biological specimens, brain autopsy and collection of selected postmortem data. (1) review the relation of neuropathologic indices to clinical diagnoses and cognition proximate to death; (2) examine the relation of risk factors to clinical outcomes; (3) examine the relation of risk factors to measures of neuropathology; and (4) summarize additional study findings. We then discuss and contextualize the study findings.
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              Cerebral small-vessel disease and decline in information processing speed, executive function and memory.

              Cerebral small-vessel disease is common in older people and may contribute to the development of dementia. The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study. Participants were 60-90 years of age and free from dementia at baseline in 1995-1996. White matter lesions (WML), cerebral infarcts and generalized brain atrophy were assessed on the baseline MRI. We performed neuropsychological testing at baseline and repeatedly in 1999-2000 and in 2001-2003. We used random-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function, information processing speed, executive function and memory. There were a total of 2266 assessments for the 832 participants in the study, with an average time from the initial to last assessment of 5.2 years. Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in cognitive function. These structural brain changes were specifically associated with decline in information processing speed and executive function. The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood. After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant. This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline. Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function.
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                Author and article information

                Contributors
                Patricia_Boyle@rush.edu
                Journal
                Ann Clin Transl Neurol
                Ann Clin Transl Neurol
                10.1002/(ISSN)2328-9503
                ACN3
                Annals of Clinical and Translational Neurology
                John Wiley and Sons Inc. (Hoboken )
                2328-9503
                01 September 2016
                October 2016
                : 3
                : 10 ( doiID: 10.1002/acn3.2016.3.issue-10 )
                : 791-800
                Affiliations
                [ 1 ] Rush Alzheimer's Disease CenterRush University Medical Center Chicago Illinois
                [ 2 ] Department of Behavioral SciencesRush University Medical Center Chicago Illinois
                [ 3 ] Department of Neurological SciencesRush University Medical Center Chicago Illinois
                [ 4 ] Department of PathologyRush University Medical Center Chicago Illinois
                [ 5 ] Department of Biomedical EngineeringIllinois Institute of Technology Chicago Illinois
                [ 6 ] Department of Diagnostic Radiology and Nuclear MedicineRush University Medical Center Chicago Illinois
                Author notes
                [*] [* ] Correspondence

                Patricia Boyle, Rush Alzheimer's Disease Center, 600 S. Paulina, Suite 1020B, Chicago, IL 60612. Tel: 312.942.8749; Fax: 312.942.2297; E‐mail: Patricia_Boyle@ 123456rush.edu

                Article
                ACN3343
                10.1002/acn3.343
                5048389
                27752514
                a5789bd1-ea77-46f4-a25c-0c9757dae274
                © 2016 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 22 February 2016
                : 27 June 2016
                : 02 August 2016
                Page count
                Figures: 4, Tables: 4, Pages: 10, Words: 6202
                Funding
                Funded by: NIA
                Award ID: R01AG17917
                Award ID: P30AG10161
                Award ID: R01AG15819
                Award ID: R01AG34374
                Award ID: R01AG40039
                Award ID: R01NS084965
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                acn3343
                October 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:04.10.2016

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