{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:24Z","timestamp":1792790364284,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,20]]},"group-title":"Neurology","reference-count":106,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["CARE-2025-2571407103"],"award-info":[{"award-number":["CARE-2025-2571407103"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Implications of menopause hormone therapy (MHT) for cognitive aging remain unclear despite decades of research. Potential reasons include insufficient consideration of MHT type, despite notable pharmacokinetic differences across formulations, and limited attention to individual differences that may exacerbate cognitive risk. We examined late-life neurocognitive outcomes as a function of\n                  <jats:italic>APOE\u03b54<\/jats:italic>\n                  status, the strongest genetic predictor of Alzheimer\u2019s disease, and MHT formulation (N=8,741). Results suggest formulation- and domain-specific association between MHT and cognition, with evidence of estradiol-based MHT providing more benefits for\n                  <jats:italic>APOE\u03b54<\/jats:italic>\n                  carriers relative to conjugated equine estrogens use. Neuroimaging analyses available for a subset of participants (N=930) revealed a consistent pattern of more favourable associations (higher volume, cortical thickness; less white matter damage) in\n                  <jats:italic>APOE\u03b54<\/jats:italic>\n                  carriers taking estradiol-based MHT. These results reframe mixed MHT findings as an issue of exposure definition and support formulation- and genetic-risk-aware approaches to menopause care.\n                <\/jats:p>","DOI":"10.64898\/2026.09.16.26363120","type":"posted-content","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:05:10Z","timestamp":1789945510000},"source":"Crossref","is-referenced-by-count":0,"title":["Associations of menopause hormone therapy with late-life cognition and brain health vary by formulation and\n                  <i>APOE\u03b54<\/i>\n                  presence"],"prefix":"10.64898","author":[{"given":"Mateja","family":"Perovi\u0107","sequence":"first","affiliation":[{"name":"Centre for Addiction and Mental Health, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Gravelsins","sequence":"additional","affiliation":[{"name":"Centre for Addiction and Mental Health, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline Wood","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada"},{"name":"Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"McGovern","sequence":"additional","affiliation":[{"name":"Centre for Addiction and Mental Health, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly J.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Rabin","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada"},{"name":"Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada"},{"name":"Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-9972","authenticated-orcid":false,"given":"Liisa A.M.","family":"Galea","sequence":"additional","affiliation":[{"name":"Centre for Addiction and Mental Health, Toronto, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092309451033000_2026.09.16.26363120v1.1","first-page":"270","article-title":"The National Alzheimer\u2019s Coordinating Center (NACC) Database: An Alzheimer Disease Database","volume":"18","year":"2004","journal-title":"Alzheimer Disease & Associated Disorders"},{"key":"2026092309451033000_2026.09.16.26363120v1.2","doi-asserted-by":"crossref","unstructured":"Morris, J. 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