The Association Between Age of Menopause and Hysterectomy Status and Alzheimer’s Disease Risk in a Cohort of Older White and Black Women

Background and Objectives: To determine whether age at menopause and premenopausal hysterectomy status are associated with incident Alzheimer's disease (AD) dementia in a group of older community-dwelling women. Materials and Methods: Participants from the Rush Memory and Aging Project, the Religious Orders Study, and the Minority Aging Research Study were included (n = 2,862, baseline age 77.1 ± 7.7 years, follow-up 8.6 ± 5.6 years, 24% Black, and 75% White). Age at menopause and premenopausal hysterectomy status were based on self-report at study entry. AD dementia diagnosis was determined annually based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. The hazard of AD dementia was evaluated using Cox-proportional regression models, with age as the time axis, adjusted for race, early life socioeconomic status, and education. To explore possible differences in risk by race, models were repeated using White and Black women propensity score-matched on age at baseline, education, and number of follow-up visits. Results: Menopause before age 45 years was associated with a 33% greater hazard of AD dementia compared with menopause after age 50 years (hazard ratio [HR] = 1.33, 95% confidence interval [CI]: 1.10-1.59). Hysterectomy was not associated with hazard of AD dementia (HR = 1.08, CI: 0.94-1.26). The association between age at menopause and hysterectomy status and AD dementia was not different for White and Black women. Conclusions: Some sex-specific menopausal characteristics, such as age at menopause, relate to the hazard of AD dementia. Given the disproportionate burden of AD in women, research is needed to explore potential mechanisms for this finding.