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Sex and Gender Driven Modifiers of Alzheimer's: The Role for Estrogenic Control Across Age, Race, Medical, and Lifestyle Risks
Rahman A, Jackson H, Hristov H, Isaacson RS, Saif N, Shetty T, Etingin O, Henchcliffe C et al.. Frontiers in aging neuroscience, 2019-11-15
Topic: Amyloid, tau and blood-test diagnosis
Research indicates that after advanced age, the major risk factor for late-onset Alzheimer's disease (AD) is female sex. Out of every three AD patients, two are females with postmenopausal women contributing to over 60% of all those affected. Sex- and gender-related differences in AD have been widely researched and several emerging lines of evidence point to different vulnerabilities that contribute to dementia risk. Among those being considered, it is becoming widely accepted that gonadal steroids contribute to the gender disparity in AD, as evidenced by the "estrogen hypothesis." This posits that sex hormones, 17β-estradiol in particular, exert a neuroprotective effect by shielding females' brains from disease development. This theory is further supported by recent findings that the onset of menopause is associated with the emergence of AD-related brain changes in women in contrast to men of the same age. In this review, we discuss genetic, medical, societal, and lifestyle risk factors known to increase AD risk differently between the genders, with a focus on the role of hormonal changes, particularly declines in 17β-estradiol during the menopause transition (MT) as key underlying mechanisms.
Key findings
- Research indicates that after advanced age, the major risk factor for late-onset Alzheimer's disease (AD) is female sex.
- This theory is further supported by recent findings that the onset of menopause is associated with the emergence of AD-related brain changes in women in contrast to men of the same age.
Why it matters
This review discusses the 'estrogen hypothesis,' which proposes that sex hormones, particularly 17β-estradiol, protect females' brains, and notes that menopause onset is associated with the emergence of Alzheimer's-related brain changes in women. It presents possible mechanisms for the higher risk in women but does not show that hormone treatment prevents or treats Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in aging neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Aging Neuroscience: journal h-index 174 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 190 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.1 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 11.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 91 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Lisa Mosconi: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Cornell University: institution h-index 1,649 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31803046) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
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Read the original
- DOI: 10.3389/fnagi.2019.00315
- PubMed: 31803046
- Original source →
- Free full text: Frontiers in Aging Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Rahman, A., Jackson, H., Hristov, H., Isaacson, R. S., Saif, N., Shetty, T., et al. (2019). Sex and Gender Driven Modifiers of Alzheimer's: The Role for Estrogenic Control Across Age, Race, Medical, and Lifestyle Risks. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2019.00315
Vancouver
Rahman A, Jackson H, Hristov H, Isaacson RS, Saif N, Shetty T, et al. Sex and Gender Driven Modifiers of Alzheimer's: The Role for Estrogenic Control Across Age, Race, Medical, and Lifestyle Risks. Frontiers in aging neuroscience. 2019. doi:10.3389/fnagi.2019.00315. PMID: 31803046.
BibTeX
@article{rahman2019-31803046,
author = {Rahman, A. and Jackson, H. and Hristov, H. and Isaacson, R. S. and Saif, N. and Shetty, T. and Etingin, O. and Henchcliffe, C. and others},
title = {{Sex and Gender Driven Modifiers of Alzheimer's: The Role for Estrogenic Control Across Age, Race, Medical, and Lifestyle Risks}},
journal = {Frontiers in aging neuroscience},
year = {2019},
doi = {10.3389/fnagi.2019.00315},
pmid = {31803046},
url = {https://doi.org/10.3389/fnagi.2019.00315}
}
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