Investigating links between white matter hyperintensities and menopausal status using robust age-correction methods in UK Biobank
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".