LONGER reproductive lifespan appears to reduce dementia risk among postmenopausal women living with type 2 diabetes.
In this nationwide cohort study, investigators analyzed 159,751 postmenopausal women with type 2 diabetes aged over 40 years who attended health examinations in 2009. Reproductive factors including age at menarche and menopause, parity and hormone replacement therapy use were collected through self-administered questionnaires. Dementia outcomes were identified using diagnostic codes together with prescriptions for antidementia medications, and Cox proportional hazards models were used to estimate associations with all cause dementia, Alzheimer disease and vascular dementia.
Reproductive Lifespan and Dementia Risk in Diabetes
Mean age at baseline was 64.5 years and mean reproductive lifespan was 33.6 years. Over a median follow up of 8.3 years, there were 24,218 cases of all cause dementia, including 18,819 cases of Alzheimer disease and 2,743 cases of vascular dementia. Compared with a reproductive lifespan shorter than 30 years, a reproductive lifespan of at least 40 years was associated with a substantially lower risk of all cause dementia, with a hazard ratio of 0.73 and a narrow confidence interval. Similar patterns were observed for both Alzheimer disease and vascular dementia, suggesting that longer endogenous estrogen exposure may be relevant across dementia subtypes.
Parity, Hormone Therapy, and Dementia Subtypes
Parity also appeared to influence dementia risk in this population. Women with parity of one had a 27% lower risk of all cause dementia compared with nulliparous women. Use of hormone replacement therapy for more than five years was associated with a 17% lower risk of all cause dementia compared with no hormone replacement therapy use. These associations again extended to both Alzheimer disease and vascular dementia, supporting a consistent relationship between reproductive factors and later life cognitive outcomes in women with type 2 diabetes.
Clinical Considerations for Postmenopausal Women
The findings highlight reproductive history and hormone replacement therapy as potential markers of dementia risk among postmenopausal women with type 2 diabetes. As this was an observational analysis based on administrative data and self report, residual confounding and misclassification remain possible. However, the large sample size and consistent associations across dementia subtypes support consideration of reproductive lifespan and related factors when discussing long term brain health in this high-risk group.
Reference: Yu J et al. Reproductive Lifespan and Reproductive Factors in Relation to Dementia Risk in Postmenopausal Women With Type 2 Diabetes. Diabetes Care. 2025;doi:10.2337/dc25-1961.
