Synergistic effects of age at menopause and vascular risk on cognitive decline in postmenopausal women
Bibliographic record
Abstract
Abstract Background Menopause‐related estrogen depletion is linked to greater vascular risk, Alzheimer’s disease (AD) pathology, and dementia risk in women. Age‐at‐menopause and vascular risk may together influence the likelihood of developing AD in women. We investigated whether earlier menopause and elevated vascular risk independently or synergistically contribute to cognitive decline in postmenopausal women compared to men. Method We used data from the Canadian Longitudinal Study on Aging. We included 7,678 postmenopausal women (mean age = 64.6±8.49 years, mean age‐at‐menopause = 50.1±5.02 years) and 7,678 age‐matched men (mean age = 64.6±8.49 years). Sex was operationalized using self‐reported sex at birth. Vascular risk was calculated using a summary score tallying the presence/absence of hypertension, diabetes, smoking, obesity, cardiovascular disease, and stroke. Participants completed cognitive assessments at baseline and 3‐year follow‐up. Self‐reported age‐at‐menopause was categorized into tertiles: early (<49), average (49‐52), and late (>52). Linear models tested independent and interactive effects of age‐at‐menopause and vascular risk on 3‐year cognition, adjusting for baseline cognition, baseline age, education, APOE4, and test language (English/French). Result In women, vascular risk and age‐at‐menopause were independently associated with cognitive decline (vascular risk: β = ‐0.107, p<.001). Relative to average age‐at‐menopause, early menopause was associated with greater cognitive decline (β = ‐0.026, p = .03), whereas late menopause was associated with less decline (β = 0.025, p = .04). In men, vascular risk was also associated with greater cognitive decline (β = ‐0.112, p<.001). Next, we examined synergistic effects of age‐at‐menopause and vascular risk in postmenopausal women. Early (vs. average) menopause and elevated vascular risk interacted to accelerate cognitive decline (β = ‐0.224, p = .002). There was no interaction between late (vs. average) menopause and vascular risk (β = ‐0.073, p = .3). In a model comparing sexes (Figure 1), vascular risk was more strongly associated with cognitive decline in women with early menopause compared to men (β = ‐0.127, p = .03). In women with average or late menopause, associations of vascular risk with cognitive decline did not significantly differ from men (average: β = ‐0.010, p = .07; late: β = ‐0.024, p = .7). Sensitivity analyses additionally adjusting for physical activity, race/ethnicity, depression, alcohol, and hormone therapy yielded similar results. Conclusion Early menopause and vascular processes may synergistically contribute to increased AD risk in women. These findings have implications for sex‐specific dementia prevention strategies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".