{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:05:56Z","timestamp":1793851556021,"version":"4.6.1"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Women face a significantly higher lifetime risk of developing Alzheimer\u2019s disease (AD) than men. This disparity is often attributed to longer female longevity, but growing evidence suggests a multifactorial origin, including hormonal, vascular, and immunologic contributions. Estrogen plays a critical neuroprotective role across multiple systems implicated in AD pathogenesis, including synaptic plasticity, mitochondrial function, and cerebrovascular integrity. However, clinical trials investigating hormone therapy (HT) for AD prevention have yielded mixed results, in part due to variability in study populations, timing of intervention, and formulation of hormones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims\/methods<\/jats:title>\n                    <jats:p>This review examines the biological rationale for estrogen\u2019s role in cognitive aging, synthesizes clinical and translational data on hormone therapy and AD risk, and highlights the importance of vascular comorbidity, including cerebral small vessel disease, in mediating AD pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We propose that estrogen\u2019s neuroprotective potential may be best realized in personalized treatment frameworks that account for age, timing, APOE genotype, and vascular burden. Interpretation of estrogen\u2019s role in AD is further complicated by variability in diagnostic criteria, which may contribute to conflicting findings across studies. Recognition of menopause-related cognitive impairment as an early, hormonally modulated risk state may offer additional opportunity for timely intervention. Addressing this complexity is essential to refining AD prevention strategies in midlife women.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2025.1634302","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:10:36Z","timestamp":1751242236000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":58,"title":["Estrogen, menopause, and Alzheimer\u2019s disease: understanding the link to cognitive decline in women"],"prefix":"10.3389","volume":"12","author":[{"given":"Nicholas","family":"Mervosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayatri","family":"Devi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5373","DOI":"10.1210\/en.2012-1458","article-title":"Estrogen receptors are found in glia and at extranuclear neuronal sites in the dorsal striatum of female rats: evidence for cholinergic but not dopaminergic colocalization","volume":"153","author":"Almey","year":"2012","journal-title":"Endocrinology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.yhbeh.2015.06.010","article-title":"Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females","volume":"74","author":"Almey","year":"2015","journal-title":"Hormones Behav."},{"key":"B3","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1177\/1534582305277152","article-title":"Effect of estrogen-serotonin interactions on mood and cognition","volume":"4","author":"Amin","year":"2005","journal-title":"Behav. 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