{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:26:39Z","timestamp":1790803599564,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"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. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Women have a higher risk of developing Alzheimer\u2019s disease (AD) than men, with hormonal changes during menopause being a potential factor. However, the exact relationship between these hormonal changes, cognitive function, and AD pathology is not fully understood. This study investigates the differential associations between serum follicle-stimulating hormone (FSH) and estradiol levels with cognitive function and cerebral amyloid-\u03b2eta (A\u03b2) deposition, quantified using amyloid positron emission tomography, in postmenopausal women across the spectrum from cognitively normal aging to AD dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 884 postmenopausal women, aged 60\u202fyears or older, were enrolled in the study. Participants were classified into three groups based on their cognitive function: cognitively normal (CN), mild cognitive impairment (MCI), and AD dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher FSH levels were associated with poorer cognitive performance and greater cerebral A\u03b2 deposition in postmenopausal women. FSH levels were highest in women with AD dementia, followed by those with MCI, and lowest in CN participants. No significant relationship was observed between estradiol levels and cognitive outcomes or A\u03b2 burden. Further analysis showed a positive correlation between FSH levels and global as well as regional cerebral A\u03b2 deposition. Mediation analysis indicated that FSH\u2019s impact on cognitive function was mediated by cerebral A\u03b2 burden. Estradiol levels, however, had no significant association with either cognitive performance or A\u03b2 pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Elevated FSH, not low E2, is linked to cognitive decline and A\u03b2 pathology in postmenopausal women. FSH may be a key risk factor for cerebral A\u03b2 deposition and cognitive decline in older women. Further research is needed to elucidate the mechanisms involved and explore hormonal interventions for AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2025.1697255","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T06:33:41Z","timestamp":1767681221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Follicle-stimulating hormone linked to cognitive decline and amyloid burden in postmenopausal women"],"prefix":"10.3389","volume":"17","author":[{"given":"Sheng-Min","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaiho","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo Hyun","family":"Um","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Woo","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunghwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Uk","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J.","family":"Aizenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-Hyun","family":"Baek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Kook","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e43053","DOI":"10.7759\/cureus.43053","article-title":"The role of estrogen therapy as a protective factor for Alzheimer's disease and dementia in postmenopausal women: a comprehensive review of the literature","volume":"15","author":"Ali","year":"2023","journal-title":"Cureus"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2024.04.08.24305450","DOI":"10.1101\/2024.04.08.24305450","article-title":"Menopausal hormone therapy and the female brain: leveraging neuroimaging and prescription registry data from the UK biobank cohort","author":"Barth","year":"2025","journal-title":"medRxiv."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.steroids.2010.01.012","article-title":"Analysis of estrogens in serum and plasma from postmenopausal women: past present, and future","volume":"75","author":"Blair","year":"2010","journal-title":"Steroids"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1196\/annals.1347.005","article-title":"Investigative models for determining hormone therapy-induced outcomes in brain: evidence in support of a healthy cell bias of estrogen action","volume":"1052","author":"Brinton","year":"2005","journal-title":"Ann. 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