{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:07:46Z","timestamp":1788883666304,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002926","name":"Cambridge University Hospitals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002926","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000735","name":"University of Cambridge","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Cerebral small vessel disease (CSVD) is associated with late\u2010onset Alzheimer's disease (LOAD) and might contribute to the relationship between apolipoprotein E \u03b54 (<jats:italic>APOE<\/jats:italic> \u03b54) and LOAD, in older people. However, it is unclear whether CSVD begins in middle age in individuals genetically predisposed to LOAD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed the relationship between radiological markers of CSVD, white matter hyperintensities and microbleeds, and genetic predisposition to LOAD in a cross\u2010sectional analysis of cognitively normal subjects aged 40\u201359 years recruited from the PREVENT Dementia study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Microbleed prevalence was 14.5%, and mean\u00a0\u00b1\u00a0standard deviation white matter hyperintensity percentage of total brain volume was 0.41\u00a0\u00b1\u00a00.28%. There was no significant association between <jats:italic>APOE<\/jats:italic> \u03b54 carrier status or history of parental dementia and white matter hyperintensity volume (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.713, .912 respectively) or microbleeds (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.082, .562 respectively) on multiple regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Genetic predisposition to LOAD, through <jats:italic>APOE<\/jats:italic> genotype or AD family history, is not associated with CSVD in middle age.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2017.08.017","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T22:30:16Z","timestamp":1511303416000},"page":"253-258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cerebral small vessel disease in middle age and genetic predisposition to late\u2010onset Alzheimer's disease"],"prefix":"10.1002","volume":"14","author":[{"given":"James D.","family":"Stefaniak","sequence":"first","affiliation":[{"name":"Manchester Academic Health Sciences Centre Salford Royal NHS Foundation Trust  Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge School of Clinical Medicine  Cambridge UK"},{"name":"China\u2010UK Centre for Cognition and Ageing Research, Faculty of Psychology Southwest University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elijah","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge School of Clinical Medicine  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Sheikh\u2010Bahaei","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Cambridge School of Clinical Medicine  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Wells","sequence":"additional","affiliation":[{"name":"The Centre for Mental Health Imperial College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Ritchie","sequence":"additional","affiliation":[{"name":"INSERM Unit 1061 Neuropsychiatry  Montpellier France"},{"name":"University of Montpellier  Montpellier France"},{"name":"Centre for Dementia Prevention, Centre for Clinical Brain Sciences University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Waldman","sequence":"additional","affiliation":[{"name":"Centre for Dementia Prevention, Centre for Clinical Brain Sciences University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Centre for Dementia Prevention, Centre for Clinical Brain Sciences University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge School of Clinical Medicine  Cambridge UK"},{"name":"Cambridgeshire and Peterborough NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.10.1531"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31829bfda4"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24647"},{"key":"e_1_2_7_5_2","doi-asserted-by":"crossref","first-page":"e001893","DOI":"10.1136\/bmjopen-2012-001893","article-title":"The PREVENT study: a prospective cohort study to identify mid\u2010life 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