{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:32:14Z","timestamp":1773293534844,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"6","funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HRS"},{"name":"NIA"},{"name":"NIH"},{"name":"IRP"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dementia incidence increases steadily with age at rates that may vary across racial groups. This racial disparity may be attributable to polygenic risk, as well as lifestyle and behavioural factors. We examined whether Alzheimer\u2019s disease polygenic score and race predict Alzheimer\u2019s disease and other related dementia incidence differentially by sex and mediation through polygenic scores for other health and behavioural conditions. We used longitudinal data from the nationally representative Health and Retirement Study. We restricted participants to those with complete data on 31 polygenic scores, including Alzheimer\u2019s disease polygenic score (2006\u20132012). Among participants aged 55 years and older in 2008, we excluded those with any memory problems between 2006 and 2008 and included those with complete follow-up on incident Alzheimer\u2019s disease and all-cause dementia, between 2010 and 2018 (N = 9683), based on self- or proxy-diagnosis every 2 years (2010, 2012, 2014, 2016 and 2018). Cox proportional hazards and 4-way decomposition models were conducted. Analyses were also stratified by sex and by race.<\/jats:p><jats:p>There were racial differences in all-cause dementia incidence (age and sex-adjusted model, per standard deviation: hazard ratio, HR = 1.34, 95% confidence interval, CI: 1.09\u20131.65, P = 0.007), partially driven by educational attainment and income. We also found independent associations of race (age and sex-adjusted model, African American versus White adults: HR = 2.07, 95% CI: 1.52\u20132.83, P &amp;lt; 0.001) and Alzheimer\u2019s disease polygenic score (age and sex-adjusted model, per SD: HR = 1.37, 95% CI: 1.00\u20131.87, P &amp;lt; 0.001) with Alzheimer\u2019s disease incidence, including sex differences whereby women had a stronger effect of Alzheimer\u2019s disease polygenic score on Alzheimer\u2019s disease incidence compared with men (P &amp;lt; 0.05 for sex by Alzheimer\u2019s disease polygenic score interaction) adjusting for race and other covariates. The total impact of Alzheimer's disease polygenic scores on Alzheimer's disease incidence was mostly direct, while the effect of race on all-cause dementia incidence was mediated through socio-economic, lifestyle and health-related factors. Finally, among the 30 polygenic scores we examined, the total effects on the pathway Alzheimer's disease polygenic score --&amp;gt; Other polygenic score --&amp;gt; Incident Alzheimer's or all-cause dementia, were statistically significant for all, driven primarily by the controlled direct effect (P&amp;lt; 0. 001). In conclusion, both race and Alzheimer\u2019s disease polygenic scores were associated independently with Alzheimer\u2019s disease and all-cause dementia incidence. Alzheimer\u2019s disease polygenic score was more strongly linked to incident Alzheimer\u2019s disease among women, while racial difference in all-cause dementia was explained by other factors including socio-economic status.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac317","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T22:43:39Z","timestamp":1669761819000},"source":"Crossref","is-referenced-by-count":9,"title":["Race, polygenic risk and their association with incident dementia among older US adults"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1050-4523","authenticated-orcid":false,"given":"May A","family":"Beydoun","sequence":"first","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP , Baltimore, MD 21224 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-3535","authenticated-orcid":false,"given":"Jordan","family":"Weiss","sequence":"additional","affiliation":[{"name":"Stanford Center on Longevity, Stanford University , CA 94305 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sri","family":"Banerjee","sequence":"additional","affiliation":[{"name":"College of Health Professions, School of Health Sciences, Walden University , Baltimore, MD 21202 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hind A","family":"Beydoun","sequence":"additional","affiliation":[{"name":"Department of Research Programs, Fort Belvoir Community Hospital , Fort Belvoir, VA 22060 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Noren Hooten","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP , Baltimore, MD 21224 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele K","family":"Evans","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP , Baltimore, MD 21224 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan B","family":"Zonderman","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP , Baltimore, MD 21224 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"issue":"8","key":"2022122208384138900_fcac317-B1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.arcmed.2012.11.003","article-title":"Epidemiology of dementias and Alzheimer's disease","volume":"43","author":"Sosa-Ortiz","year":"2012","journal-title":"Arch Med 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