{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:11:48Z","timestamp":1790727108603,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["334047"],"award-info":[{"award-number":["334047"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1127060"],"award-info":[{"award-number":["1127060"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older individuals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by\n                    <jats:italic>APOE<\/jats:italic>\n                    genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrolment, participants had no history of diagnosed dementia, cardiovascular disease, physical disability or cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a &gt;1.5 standard deviation decline in test score for either global cognition, episodic memory, language\/executive function or psychomotor speed, versus baseline scores. Cumulative incidence for all\u2010cause dementia and cognitive decline was calculated with mortality as a competing event, stratified by\n                    <jats:italic>APOE<\/jats:italic>\n                    genotypes and tertiles of a PRS based on 23 common non\u2010\n                    <jats:italic>APOE<\/jats:italic>\n                    variants. During a median 4.5\u00a0years of follow\u2010up, 324 participants developed dementia, 503 died. Cumulative incidence of dementia to age 85\u00a0years was 7.4% in all participants, 12.6% in\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b53\/\u03b54 and 26.6% in \u03b54\/\u03b54.\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 heterozygosity\/homozygosity was associated with a 2.5\/6.3\u2010fold increased dementia risk and 1.4\/1.8\u2010fold cognitive decline risk, versus \u03b53\/\u03b53 (\n                    <jats:italic>p\u00a0<\/jats:italic>\n                    &lt;\u00a00.001 for both). High PRS tertile was associated with a 1.4\u2010fold dementia risk versus low (CI 1.04\u20131.76,\n                    <jats:italic>p\u00a0<\/jats:italic>\n                    =\u00a00.02), but was not associated with cognitive decline (CI 0.96\u20131.22,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.18). Incidence of dementia among healthy older individuals is low across all genotypes; however,\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 and high PRS increase relative risk.\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 is associated with cognitive decline, but PRS is not.\n                  <\/jats:p>","DOI":"10.1111\/acel.13384","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:59:19Z","timestamp":1622077159000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5858-3788","authenticated-orcid":false,"given":"Moeen","family":"Riaz","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aamira","family":"Huq","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"},{"name":"Department of Genomic Medicine Royal Melbourne Hospital University of Melbourne Melbourne Vic Australia"},{"name":"Department of Medicine Royal Melbourne Hospital University of Melbourne Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne G","family":"Orchard","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Tiller","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lockery","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn L.","family":"Woods","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan E.","family":"Renton","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience and Ronald Loeb Center for Alzheimer\u2019s Disease Icahn School of Medicine at Mount Sinai New York NY USA"},{"name":"Departments of Neurology and Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Goate","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience and Ronald Loeb Center for Alzheimer\u2019s Disease Icahn School of Medicine at Mount Sinai New York NY USA"},{"name":"Departments of Neurology and Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sebra","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn Institute for Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Schadt","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn Institute for Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Brodtmann","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health Melbourne Vic Australia"},{"name":"Melbourne Dementia Research Centre University of Melbourne Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj C.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Family Medicine and Rush Alzheimer's Disease Center Rush University Medical Center Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsdon","family":"Storey","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Murray","sequence":"additional","affiliation":[{"name":"Berman Center for Outcomes and Clinical Research Hennepin Healthcare Research Institute University of Minnesota Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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