Prior endogenous and exogenous estrogen and incident dementia in the 10th decade of life: The 90+ Study

Objective: This study aimed to investigate the association of endogenous and exogenous estrogen exposure with risk of incident dementia in the oldest-old (age 90+ years).Methods: Participants were part of The 90+ Study, a longitudinal study begun in 2003 of aging and dementia among people aged 90+ years. Menstrual, reproductive, and menopausal data were collected in the 1980s as part of the population-based Leisure World Cohort Study. Cognitive status at baseline was determined from an in-person neurological evaluation with biannual follow-up through June 2019. Hazard ratios (HRs) of dementia associated with estrogen-related variables were estimated using Cox regression analysis. No adjustment was made for multiple comparisons.Results: A total of 424 women without dementia at baseline had at least one follow-up evaluation. The mean age was 68.5 years at enrollment in the Leisure World Cohort Study, 93.2 years at enrollment in The 90+ Study, and 96.5 years at last follow-up. During follow-up (mean 3.4 years) dementia was diagnosed in 209 (49%) participants. No individual menstrual, reproductive, menopausal, or estrogen replacement variable was associated with risk of incident dementia after age 90 years. However, women with a high endogenous estrogen exposure index (summarizing exposure from menarche to menopause) had a non-significant 25% lower risk (HR = 0.75, 95% confidence interval 0.53-1.06).Conclusions: Prior exposure to estrogen, endogenous or exogenous, had little effect on risk of dementia in the 10th decade of life.