Adverse childhood experiences, early menopause, cognition, and dementia in older adults in the United States.

BACKGROUND: Adverse childhood experiences (ACEs) may accelerate early menopause and influence neurodegenerative processes, contributing to sex-specific dementia risk. This study examined associations with cognitive decline and incident dementia in ACEs and early menopause.

METHODS: We studied 6093 women and 5784 men aged ≥50 years from the Health and Retirement Study, a US cohort spanning between 2010 and 2022. Incident dementia was based on self-report of physician-diagnosed dementia. Cognition was measured using a composite score of immediate and delayed recall, serial sevens subtraction, and counting backwards (range, 0-27). ACEs were assessed using seven items and classified into none, 1, 2, and ≥3 ACEs. Age at menopause was classified into <47, 47 to 52, and ≥53 years. We included men and defined the four categories of sex and age at menopause, assessing varying levels of female hormones with age at menopause serving as the proxy indicator of those differences. Covariates included lifestyle risk factors for dementia. We used a longitudinal panel design with each observation containing baseline covariates and 2-year follow-up outcomes. We applied a random-effects model to survival analysis for incident dementia and to linear regression analysis for cognition.

RESULTS: Here we show that experiencing 2 (hazard ratio: 1.32 [95% CI: 1.07-1.62]) or ≥3 ACEs (1.32 [1.03-1.68]) is associated with higher dementia risk compared with no ACEs. Dementia risk does not differ by sex and age at menopause in women. Women with early menopause ( = -0.22 [95%CI: -0.41 to -0.03]) and men (-0.92 [-1.06 to -0.78]) have worse cognition than women with late menopause. ACE level is not associated with cognition. No mediation by early menopause is observed between multiple ACEs, dementia, or cognition in women.

CONCLUSIONS: Mechanisms linking ACEs and early menopause to dementia risk may differ. Risk reduction strategies should consider preventing and addressing ACEs and early menopause, respectively.