Reproductive Lifespan and Reproductive Factors in Relation to Dementia Risk in Postmenopausal Women With Type 2 Diabetes

OBJECTIVE Endogenous estrogen exposure has been linked to a reduced risk of cognitive de-cline. Our study examined the influence of reproductive factors on the risk of dementia among women with diabetes. RESEARCH DESIGN AND METHODS We identified 159,751 postmenopausal women with type 2 diabetes aged over 40 years who underwent health examinations in 2009 from the National Health Information Database. Data on reproductive factors were obtained using self-administered questionnaires. Incident dementia was determined by diagnosis codes and records of antidementia medication prescriptions. Cox proportional hazards regression analyses estimated the risk of all-cause dementia, Alzheimer disease, and vascular dementia according to reproductive factors such as reproductive lifespan, parity, and hormone replacement therapy (HRT) use. RESULTS The mean age was 64.5 ± 8.0 years, and the mean reproductive lifespan was 33.6 ± 4.5 years. Over a median follow-up of 8.3 years, 24,218 cases of all-cause dementia were identified (18,819 cases of Alzheimer disease, 2,743 cases of vascular dementia). Compared with a reproductive lifespan of <30 years, ≥40 years was associated with lower risk of all-cause dementia (hazard ratio 0.73; 95% CI 0.69–0.78). Women with parity 1 had a 27% lower risk of all-cause dementia compared with women with parity 0, and women who used HRT for more than 5 years had a 17% lower risk compared with those who did not use HRT. Comparable effects were found for both Alzheimer disease and vascular dementia. CONCLUSIONS A longer reproductive lifespan was linked to a reduced risk of dementia in post-menopausal women with type 2 diabetes.