Abstract EP67: Early Menopause Is Linked To Increased Risk Of Presenile Dementia Before Age 65 Years

Abstract

Introduction: Evidence on the association between age at menopause and risk of dementia has been inconsistent. Some studies observed that later menopause was related to lower risk of dementia, while others reported no association, or even came to the opposite. Estradiol plays an important role in a wide range of neurological functions in brain, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative diseases, and accelerate the progression of dementia. Hypothesis: Based on the neuroprotective effects of estrogen, we hypothesized that earlier menopause might be related to higher risk of and earlier onset of dementia, compared with menopause at normal age or later. Methods: We used cohort data from UK Biobank and a total of 153 291 postmenopausal women were included. Age at menopause was categorized as <40 (premature), 40-44 (early), 45-49, 50-51 (reference), 52-55, and >55 years. The main outcome was all-cause dementia, a comprehensive outcome including Alzheimer's disease (AD), vascular dementia (VD) and dementia classified elsewhere. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) on the association between menopausal age and all-cause dementia. We also stratified the age when dementia was diagnosed into ≤65 years and >65 years to explore the association between age at menopause and timing of experiencing dementia. All HRs were adjusted for age at last follow-up, race, education level, BMI, cigarette smoking, alcohol drinking, cardiovascular disease status, diabetes status, income, leisure activities and physical activities. We also used restricted cubic splines to analyze the dose-response relationship between menopausal age and dementia. Results: Among the 153 291 women, there were 1688 woman suffering from all-cause dementia. The average follow-up time was 11.7 years. Compared with menopausal age of 50-51 years, the HRs (95% CI) with dementia in women with menopausal age <40, 40-44, 45-49, 52-55 and >55 years were 1.53 (1.22-1.91), 1.07 (0.89-1.28), 1.08 (0.94-1.25), 0.81 (0.70-0.94), and 0.91 (0.78-1.06) respectively. Restricted cubic spline also showed an inverse dose-response relationship between them. In addition, compared to women with menopausal age of 50-51 years, women with early menopause (<45 years) had elevated risk of experiencing all-caused dementia before age 65 years (1.31, 1.07-1.72; P <0.001). Conclusions: Compared to women with menopausal age of 50-51 years, women with premature menopause (<40 years) had around 35% higher risk of having all-cause dementia, and women with early menopause (<45 years) were 1.3 times more likely to experience presenile dementia before age 65 years. Women with early menopause may need a close monitoring of their cognitive decline in clinical practice.