Perimenopause: A critical window to intervene to reduce the risk of cognitive impairment in females
Bibliographic record
Abstract
Abstract Background Two‐thirds of all persons with late‐onset Alzheimer’s disease (AD) are female. The transition to menopause, or perimenopause, negatively impacts the female brain and is proposed to contribute to a female’s greater lifetime risk for dementia. Declining 17‐β estradiol levels during perimenopause is associated with markers of AD pathology, such as reduced cerebral glucose metabolism. Preliminary evidence suggests APOE4‐positive perimenopausal females have greater amyloid In cognitively normal individuals, the T1‐weighted and T2‐weighted (T1w/T2w) ratio from magnetic resonance imaging can be used as a non‐invasive proxy measure of amyloid‐β deposition. Specifically, higher T1w/T2w ratios are associated with higher amyloid‐β accumulation in cognitively normal individuals. Thus, to better understand the impact of perimenopause on the female brain and cognitive health, we compared the T1w/T2w ratio, hippocampal volume, and cognitive performance in perimenopausal females vs. aged‐matched males. Methods Data was acquired from the Human Connectome Project. We included 44 perimenopausal females, defined by the Stages of Reproductive Aging Workshop + 10 Staging System, and 44 age‐matched males. Executive function was measured by the Flanker Task in the NIH Toolbox Cognition Battery and data were available for all 88 individuals. Hippocampal volume data were available for 23/44 perimenopausal females and 27/44 age‐matched males. T1w/T2w neuroimaging data were available for 19/44 perimenopausal females and 27/44 age‐matched males. Between‐group differences in these measures of interest were determined by analysis of covariance (ANCOVA). For the Flanker Task ANCOVA model, the Montreal Cognitive Assessment score and free estrogen levels were included as covariates. For hippocampal volume model, intracranial volume was included as a covariate. For the T1w/T2w ratio model, the Pittsburgh Sleep Quality Inventory score was included as a covariate. Results Perimenopausal females performed significantly worse vs. their male counterparts on the Flanker Test (mean difference: ‐28.194; p = .000). Compared with age‐matched males, perimenopausal females had a significantly smaller hippocampal volume (mean difference: ‐544.829; p = .033) and higher T1w/T2w (mean difference: 0.290; p = .042). Conclusion Our results support the hypothesis that the menopause transition is a critical window to intervene to reduce the risk of cognitive impairment in females.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".