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      Asymptomatic Cerebral Small Vessel Disease: Insights from Population-Based Studies

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          Abstract

          Cerebral small vessel disease (CSVD) is a common group of neurological conditions that confer a significant burden of morbidity and mortality worldwide. In most cases, CSVD is only recognized in its advanced stages once its symptomatic sequelae develop. However, its significance in asymptomatic healthy populations remains poorly defined. In population-based studies of presumed healthy elderly individuals, CSVD neuroimaging markers including white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, cortical superficial siderosis, and cerebral microinfarcts are frequently detected. While the presence of these imaging markers may reflect unique mechanisms at play, there are likely shared pathways underlying CSVD. Herein, we aim to assess the etiology and significance of these individual biomarkers by focusing in asymptomatic populations at an epidemiological level. By primarily examining population-based studies, we explore the risk factors that are involved in the formation and progression of these biomarkers. Through a critical semi-systematic review, we aim to characterize “asymptomatic” CSVD, review screening modalities, and draw associations from observational studies in clinical populations. Lastly, we highlight areas of research (including therapeutic approaches) in which further investigation is needed to better understand asymptomatic CSVD.

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          Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

          The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
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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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              Incidental findings on brain MRI in the general population.

              Magnetic resonance imaging (MRI) of the brain is increasingly used both in research and in clinical medicine, and scanner hardware and MRI sequences are continually being improved. These advances are likely to result in the detection of unexpected, asymptomatic brain abnormalities, such as brain tumors, aneurysms, and subclinical vascular pathologic changes. We conducted a study to determine the prevalence of such incidental brain findings in the general population. The subjects were 2000 persons (mean age, 63.3 years; range, 45.7 to 96.7) from the population-based Rotterdam Study in whom high-resolution, structural brain MRI (1.5 T) was performed according to a standardized protocol. Two trained reviewers recorded all brain abnormalities, including asymptomatic brain infarcts. The volume of white-matter lesions was quantified in milliliters with the use of automated postprocessing techniques. Two experienced neuroradiologists reviewed all incidental findings. All diagnoses were based on MRI findings, and additional histologic confirmation was not obtained. Asymptomatic brain infarcts were present in 145 persons (7.2%). Among findings other than infarcts, cerebral aneurysms (1.8%) and benign primary tumors (1.6%), mainly meningiomas, were the most frequent. The prevalence of asymptomatic brain infarcts and meningiomas increased with age, as did the volume of white-matter lesions, whereas aneurysms showed no age-related increase in prevalence. Incidental brain findings on MRI, including subclinical vascular pathologic changes, are common in the general population. The most frequent are brain infarcts, followed by cerebral aneurysms and benign primary tumors. Information on the natural course of these lesions is needed to inform clinical management. Copyright 2007 Massachusetts Medical Society.
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                Author and article information

                Journal
                J Stroke
                J Stroke
                JOS
                Journal of Stroke
                Korean Stroke Society
                2287-6391
                2287-6405
                May 2019
                17 April 2019
                : 21
                : 2
                : 121-138
                Affiliations
                [a ]Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
                [b ]Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
                [c ]Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
                [d ]Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands
                [e ]Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
                [f ]Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
                Author notes
                Correspondence: Anand Viswanathan J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge Street, Suite 300, Boston, MA 02114, USA Tel: +1-617-643-3876 Fax: +1-617-726-5346 E-mail: aviswanathan1@ 123456partners.org
                Article
                jos-2018-03608
                10.5853/jos.2018.03608
                6549070
                30991799
                90d70e01-e48d-4e01-b378-a1dcdfc44e18
                Copyright © 2019 Korean Stroke Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 December 2018
                : 30 January 2019
                : 28 February 2019
                Categories
                Review

                cerebral small vessel diseases,epidemiology,stroke, lacunar,leukoaraiosis

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