Home › Research › Vascular contributions
Investigating links between white matter hyperintensities and menopausal status using robust age-correction methods in UK Biobank
Denise Wezel, Olivier Parent, Manuela Costantino, Lina Sifi, Grace Pigeau, Nicole J Gervais, Ann McQuarrie, Josefina Maranzano et al.. Brain Communications, 2025-01-01
Topic: Brain proteins, microglia and lab models
Abstract White matter hyperintensities (WMHs) are radiological abnormalities indicative of cerebrovascular dysfunction associated with increased risk for cognitive decline. WMHs increase in prevalence with older age, and there are known sex differences as older women harbour higher WMH burden than men. Some have hypothesized that the increase in this dementia-related risk factor is related to the menopausal transition. To untangle the effects of age and menopause, we leveraged a large cross-sectional sample of women from the UK Biobank (n = 9560) to investigate differences in WMH volumes across menopausal status using a strict age-matching procedure. Surprisingly, we find higher WMH volumes in premenopausal women compared to postmenopausal women in certain analysis schemes, especially as compared to surgically postmenopausal women. These results reached significance mostly in analyses where the postmenopausal groups had a longer time since menopause. Our results pertaining to menopause-related characteristics, such as age at menopause or menopause hormonal therapy, did not replicate the literature reporting an association with WMH volumes. Cardiometabolic factors, such as smoking and blood pressure, were significant predictors of WMH volume in the full sample without age-matching. These effects were not significantly different across menopausal status, with the exception of blood pressure medication use, which was associated with higher WMH volumes to a larger extent in premenopausal women relative to postmenopausal women. Our findings are in the opposite direction of reported effects of higher WMH volumes following the menopausal transition, which could be due to variations in age correction techniques or idiosyncrasies in the UK Biobank sample, especially as it relates to the lack of data on perimenopause. We further show that the effects of positive cardiometabolic and lifestyle factors on brain health, as indexed with WMH volumes, generally do not change after menopause. Factors other than the menopausal status may be at play in explaining the difference in WMH burden between men and women in later life.
Key findings
- Abstract White matter hyperintensities (WMHs) are radiological abnormalities indicative of cerebrovascular dysfunction associated with increased risk for cognitive decline.
- Surprisingly, we find higher WMH volumes in premenopausal women compared to postmenopausal women in certain analysis schemes, especially as compared to surgically postmenopausal women.
- These results reached significance mostly in analyses where the postmenopausal groups had a longer time since menopause.
- Our results pertaining to menopause-related characteristics, such as age at menopause or menopause hormonal therapy, did not replicate the literature reporting an association with WMH volumes.
- Cardiometabolic factors, such as smoking and blood pressure, were significant predictors of WMH volume in the full sample without age-matching.
Why it matters
In this cross-sectional UK Biobank sample, higher white matter hyperintensity volumes were found in premenopausal women compared to postmenopausal women in some analyses, and menopause-related characteristics such as age at menopause or hormone therapy did not show the previously reported associations with WMH volume. These findings question the idea that the menopausal transition directly drives this dementia-related risk factor, but the study cannot show cause and effect.
Study details
- Study designcross-sectional
- Participants9,560
- Evidence strengthLow
How this study scored 49/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain Communications) |
| Journal's citation record | 0 / 4 | Brain Communications: journal h-index 67 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 3 / 4 | 9,560 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author M. Mallar Chakravarty: h-index 84 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Chicago: institution h-index 1,769 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41426431) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1093/braincomms/fcaf475
- PubMed: 41426431
- Original source →
- Free full text: Brain Communications →
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
Wezel, D., Parent, O., Costantino, M., Sifi, L., Pigeau, G., Gervais, N. J., et al. (2025). Investigating links between white matter hyperintensities and menopausal status using robust age-correction methods in UK Biobank. Brain Communications. https://doi.org/10.1093/braincomms/fcaf475
Vancouver
Wezel D, Parent O, Costantino M, Sifi L, Pigeau G, Gervais NJ, et al. Investigating links between white matter hyperintensities and menopausal status using robust age-correction methods in UK Biobank. Brain Communications. 2025. doi:10.1093/braincomms/fcaf475. PMID: 41426431.
BibTeX
@article{wezel2025-41426431,
author = {Wezel, Denise and Parent, Olivier and Costantino, Manuela and Sifi, Lina and Pigeau, Grace and Gervais, Nicole J and McQuarrie, Ann and Maranzano, Josefina and others},
title = {{Investigating links between white matter hyperintensities and menopausal status using robust age-correction methods in UK Biobank}},
journal = {Brain Communications},
year = {2025},
doi = {10.1093/braincomms/fcaf475},
pmid = {41426431},
url = {https://doi.org/10.1093/braincomms/fcaf475}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.
Related studies in Vascular contributions
Also tagged “cerebral”
900 studies in the library carry the topic tag “cerebral”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 900 tagged studies.