Sex Hormones and Cerebrovascular Health: Implications for Dementia Risk Across the Lifespan
Bibliographic record
Abstract
Abstract Background Circulating sex hormones decrease in aging, influencing cerebrovascular health, a key factor in dementia risk. Early menopause is a risk factor for dementia comparable to smoking 2 . Estradiol consistently supports female vasculature 1 and brain health, though its effects on cerebrovascular health is understudied. Testosterone’s effects in males remain unclear 3,4 . Limited data exist on the sex‐ and life stage‐specific impacts of hormones on cerebrovascular health, making it critical to understand these relationships for targeting hormone‐related interventions to mitigate dementia risk Method 187 females from the Human Connectome Aging Project were categorized according to STRAW criteria as reproductive ( n = 65), perimenopausal ( n = 29) or postmenopausal ( n = 93). 157 males were as younger [36 to 49 years] ( n = 60) or older [50 to 70 years] ( n = 97). MRI scans quantified cerebral blood flow (CBF), arterial transit time (ATT), relative cerebrovascular reactivity (CVR) 5 and a blood draw for circulating sex hormones. ANCOVA’s tested group differences, and polynomial regressions assessed hormone relationships with CBF, ATT, and CVR. Result In reproductive females, testosterone exhibited a U‐shaped relationship with CVR in the temporal lobe. Perimenopausal females demonstrated an inverse relationship between estradiol and ATT (shorter ATT indicates better cerebrovascular health) in frontal and temporal regions, and a positive relationship with testosterone and ATT in temporal and hippocampal regions. Postmenopausal females revealed inverse linear relationships with testosterone and CBF in frontal and temporal regions, and with CVR in frontal regions. In males, testosterone positively correlated with CBF in younger participants, while estradiol inversely correlated with CBF in older males. Conclusion Sex hormones demonstrate life stage‐ and sex‐specific associations with cerebrovascular health including CBF, CVR, and ATT, all crucial factors in dementia pathogenesis. Both sexes had opposite directions of relationship for estradiol and testosterone. Estradiol was associated with better cerebrovascular health (shorter ATT in perimenopausal females), while testosterone showed negatives effects in females (longer ATT, lower CBF and CVR). Conversely, testosterone was associated with higher CBF in younger males and estradiol lower CBF in older males. These findings underscore the potential for hormone‐targeted strategies to support cerebrovascular health and reduce dementia risk through age and stage‐specific interventions.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".