ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
This article is part of the Research TopicWomen in Aging Neuroscience: Neurodegenerative DisordersView all articles
Follicle-Stimulating Hormone Linked to Cognitive Decline and Amyloid Burden in Postmenopausal Women
Provisionally accepted
Sheng-Min Wang1
Chaiho Jeong1
Yoo Hyun Um1Dong Woo Kang1
Sunghwan Kim1Soyoung Lee2
Chang Uk Lee1Howard J Aizenstein3
Ki-hyun Baek1
Hyun Kook Lim1*- 1Catholic University of Korea, Seoul, Republic of Korea
- 2Harvard Medical School, Boston, United States
- 3University of Pittsburgh Alzheimer's Disease Research Center, Pittsburgh, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Women have a higher risk of developing Alzheimer's 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-βeta (Aβ) deposition, quantified using amyloid positron emission tomography, in postmenopausal women across the spectrum from cognitively normal aging to AD dementia. A total of 884 postmenopausal women, aged 60 years 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. Higher FSH levels were associated with poorer cognitive performance and greater cerebral Aβ 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 Aβ burden. Further analysis showed a positive correlation between FSH levels and global as well as regional cerebral Aβ deposition. Mediation analysis indicated that FSH's impact on cognitive function was mediated by cerebral Aβ burden. Estradiol levels, however, had no significant association with either cognitive performance or Aβ pathology. Elevated FSH, not low E2, is linked to cognitive decline and Aβ pathology in postmenopausal women. FSH may be a key risk factor for cerebral Aβ deposition and cognitive decline in older women. Further research is needed to elucidate the mechanisms involved and explore hormonal interventions for AD.
Keywords: Follicle-stimulating hormone, estrogen, cognitive impairment, Amyloid retention, Alzheimer's disease
Received: 02 Sep 2025; Accepted: 21 Nov 2025.
Copyright: © 2025 Wang, Jeong, Um, Kang, Kim, Lee, Lee, Aizenstein, Baek and Lim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hyun Kook Lim, drblues@catholic.ac.kr
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.