{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:25:50Z","timestamp":1777353950034,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:00:00Z","timestamp":1704499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>We estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle\u2010aged and older adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Among 45,616 dementia\u2010free participants aged 45\u201380, linear regressions tested whether genetic risk score for AD (AD\u2010GRS) had age\u2010dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>AD\u2010GRS modified the estimated effect of age (per decade) on the amygdala (\u22120.41 mm<jats:sup>3<\/jats:sup> [\u22120.42, \u22120.40]); hippocampus (\u22120.45 mm<jats:sup>3<\/jats:sup> [\u22120.45, \u22120.44]), nucleus accumbens (\u22120.55 mm<jats:sup>3<\/jats:sup> [\u22120.56, \u22120.54]), thalamus (\u22120.38 mm<jats:sup>3<\/jats:sup> [\u22120.39, \u22120.37]), and medial orbitofrontal cortex (\u22120.23 mm<jats:sup>3<\/jats:sup> [\u22120.24, \u22120.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD\u2010GRS excluding apolipoprotein E (<jats:italic>APOE<\/jats:italic>) was additionally associated with entorhinal and middle temporal cortices.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p><jats:italic>APOE<\/jats:italic> and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13610","type":"journal-article","created":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T08:29:16Z","timestamp":1704529756000},"page":"1978-1987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants"],"prefix":"10.1002","volume":"20","author":[{"given":"Peter T.","family":"Buto","sequence":"first","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics University of California  San Francisco California USA"},{"name":"Department of Epidemiology Boston University School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingxuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics University of California  San Francisco California USA"},{"name":"Department of Epidemiology Boston University School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renaud","family":"La Joie","sequence":"additional","affiliation":[{"name":"Memory and Aging Center University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott C.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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