{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:59:58Z","timestamp":1791644398846,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015595","name":"GHR Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARF\u201023\u20101151259"],"award-info":[{"award-number":["AARF\u201023\u20101151259"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Women show higher levels of Alzheimer's disease (AD) pathology than men, but the implications for cognitive decline remain unclear. Determining the extent to which tau burden differentially accelerates cognitive decline in men and women will provide critical insights into sex\u2010specific pathways of disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We leveraged tau positron emission tomography (PET), amyloid beta (A\u03b2) PET, apolipoprotein E (\n                      <jats:italic>APOE)<\/jats:italic>\n                      \u03b54 genotyping, and longitudinal cognitive data over approximately 8.6 (standard deviation [SD]\u00a0=\u00a03.8) years from 1007 cognitively unimpaired adults across three cohorts. Cognitive trajectories were modeled with linear mixed\u2010effects regression including sex\u00a0\u00d7\u00a0tau\u00a0\u00d7\u00a0time interactions, and results were synthesized using random\u2010effects meta\u2010analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Higher tau burden in medial and lateral temporal regions was associated with faster cognitive decline in women than in men.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>High tau burden carries a disproportionately greater cognitive cost for women, underscoring the need for sex\u2010specific approaches to early detection and therapeutic intervention in AD.<\/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>A meta\u2010analysis across three independent cohorts shows that female cognitive advantage at low tau shifts to vulnerability at higher tau.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Sex differences in tau\u2010related cognitive decline were consistent after accounting for amyloid burden.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Sex\u2010specific rates of cognitive decline should be considered in clinical trial design.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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