Hormone replacement therapy in women and vascular risk factors modify the association of a multi‐ancestry polygenic risk score with Alzheimer disease and related traits
Nuzulul Kurniansyah, Shinya Tasaki, Congcong Zhu, John Joseph Farrell, Habbiburr Rehman, Richard Sherva, Richard L. Hauger, Victoria C. Merritt et al.. Alzheimer s & Dementia, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
The AD PRS was associated with AD in the ADSP sample, with odds ratios per standard deviation ranging from 1.14 to 1.52 across ancestry groups and robust validation in independent cohorts (Figure 1). Stratified analyses showed that the association between PRS and AD risk was stronger among individuals with vascular comorbidities (Figure 2), suggesting that long-term poor vascular health may amplify polygenic risk for AD. The AD PRS was also associated with memory, executive function, and language performance, and sex-specific differences in memory score observed among EA individuals. Among individuals with a high PRS (top tertile of the PRS distribution), ever-users of HRT exhibited better memory trajectories over time compared to never-users. Timing played a crucial role: HRT initiation within five years of menopause was associated with higher memory scores (β = 0.24, p = 3.05×10⁻³; Figure 3A). Trajectory analyses indicated that the association between HRT and memory was most prominent in midlife and attenuated in later years (Figure 3B). AD PRS was also associated with AD-related brain MRI measures, suggesting its contribution to early structural changes linked to AD. Our findings demonstrate the utility of an ancestry-aware PRS for advancing understanding of AD in diverse populations. Future research incorporating AD PRS in studies of sex-specific, vascular, and hormonal risk factors may offer promise for personalized interventions and prevention strategies for AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Kurniansyah, N., Tasaki, S., Zhu, C., Farrell, J. J., Rehman, H., Sherva, R., et al. (2025). Hormone replacement therapy in women and vascular risk factors modify the association of a multi‐ancestry polygenic risk score with Alzheimer disease and related traits. Alzheimer s & Dementia. https://doi.org/10.1002/alz70861_108536
Vancouver
Kurniansyah N, Tasaki S, Zhu C, Farrell JJ, Rehman H, Sherva R, et al. Hormone replacement therapy in women and vascular risk factors modify the association of a multi‐ancestry polygenic risk score with Alzheimer disease and related traits. Alzheimer s & Dementia. 2025. doi:10.1002/alz70861_108536. PMID: 41434242.
BibTeX
@article{kurniansyah2025-41434242,
author = {Kurniansyah, Nuzulul and Tasaki, Shinya and Zhu, Congcong and Farrell, John Joseph and Rehman, Habbiburr and Sherva, Richard and Hauger, Richard L. and Merritt, Victoria C. and others},
title = {{Hormone replacement therapy in women and vascular risk factors modify the association of a multi‐ancestry polygenic risk score with Alzheimer disease and related traits}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70861_108536},
pmid = {41434242},
url = {https://doi.org/10.1002/alz70861_108536}
}
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.
Key findings
- The AD PRS was associated with AD in the ADSP sample, with odds ratios per standard deviation ranging from 1.14 to 1.52 across ancestry groups and robust validation in independent cohorts (Figure 1).
- Stratified analyses showed that the association between PRS and AD risk was stronger among individuals with vascular comorbidities (Figure 2), suggesting that long-term poor vascular health may amplify polygenic risk for AD.
- The AD PRS was also associated with memory, executive function, and language performance, and sex-specific differences in memory score observed among EA individuals.
- Among individuals with a high PRS (top tertile of the PRS distribution), ever-users of HRT exhibited better memory trajectories over time compared to never-users.
- Timing played a crucial role: HRT initiation within five years of menopause was associated with higher memory scores (β = 0.24, p = 3.05×10⁻³; Figure 3A).
Why it matters
A polygenic risk score was associated with Alzheimer disease across ancestry groups, and the association was stronger in people with vascular conditions. Among women with high genetic risk, ever-use of hormone replacement therapy was linked to better memory trajectories, especially when started within five years of menopause, but this is an observational finding, not proof of a treatment effect.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 38/100
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 (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 4 / 5 | 2025 — within 3 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Lindsay A. Farrer: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 20 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41434242) |
| Free to read | 2 / 2 | Free to read |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70861_108536
- PubMed: 41434242
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Genetics
Also tagged “precursor”
1,337 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,337 tagged studies.