{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:03:40Z","timestamp":1789556620691,"version":"build-2803163510"},"reference-count":75,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG066468"],"award-info":[{"award-number":["P30 AG066468"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000064","name":"National Center for Complementary and Alternative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000064","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":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Many complex traits and diseases show sex\u2010specific biases in clinical presentation and prevalence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>To understand sex\u2010specific genetic architecture of cognitive decline across five cognitive domains (attention, memory, executive function, language, and visuospatial function) and global cognitive function, we performed sex\u2010stratified genome\u2010wide meta\u2010analysis in 3021 older adults aged \u2265 65 years (female\u00a0=\u00a01545, male\u00a0=\u00a01476) from three prospective cohorts. Gene\u2010based and gene\u2010set enrichment analyses were conducted for each cognitive trait.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We identified a novel genome\u2010wide significant (GWS) intergenic locus for decline of memory in males near\n                      <jats:italic>RPS23P3<\/jats:italic>\n                      on chromosome 4 (rs6851574: minor allele frequency [MAF]\u00a0=\u00a00.39,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>male<\/jats:sub>\n                      \u00a0=\u00a04.10E\u201008,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      <jats:sub>male<\/jats:sub>\n                      \u00a0=\u00a00.19;\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      \u00a0=\u00a03.76E\u201004). We also identified a subthreshold GWS locus for decline of executive function on chromosome 12 in females near the\n                      <jats:italic>NDUFA12<\/jats:italic>\n                      gene, involved in oxidative phosphorylation (rs11107823: MAF\u00a0=\u00a00.12,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>female<\/jats:sub>\n                      \u00a0=\u00a09.35E\u201008,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      <jats:sub>female<\/jats:sub>\n                      \u00a0=\u00a00.28;\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      \u00a0=\u00a07.42E\u201006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Sex\u2010aware genetic studies can help in the identification of novel genetic loci and enhance sex\u2010specific understanding of cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Our genome\u2010wide meta\u2010analysis of single variants identified two new genetic associations, one in males and one in females.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The novel male association was observed with the decline of memory in the intergenic region near the\n                            <jats:italic>RPS23P3<\/jats:italic>\n                            gene on chromosome 4. This intergenic region has previously been implicated in several brain and cognition related traits, including anatomical brain aging, brain shape, and educational attainment.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The novel female\u2010specific association was observed with decline in executive function on chromosome 12 near the\n                            <jats:italic>NDUFA12<\/jats:italic>\n                            gene, which is involved in oxidative phosphorylation.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Sex\u2010stratified analyses offer sex\u2010specific understanding of biological pathways involved in cognitive aging.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14461","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T11:14:51Z","timestamp":1741605291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sex\u2010stratified genome\u2010wide meta\u2010analysis identifies novel loci for cognitive decline in older adults"],"prefix":"10.1002","volume":"21","author":[{"given":"Vibha","family":"Acharya","sequence":"first","affiliation":[{"name":"Department of Human Genetics University of Pittsburgh School of Public Health  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang\u2010Hsien","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Pittsburgh School of Public Health  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth E.","family":"Snitz","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Ganguli","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Psychiatry School of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Epidemiology University of Pittsburgh School of Public Health  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T.","family":"DeKosky","sequence":"additional","affiliation":[{"name":"McKnight Brain Institute and Department of Neurology College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar L.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Feingold","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Pittsburgh School of Public Health  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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