Association between age at menopause and 14-year cognitive trajectories in the English Longitudinal Study of Ageing

IntroductionThe association between age at menopause and long-term cognitive decline remains largely unknown. We examined the association between age at menopause and 14-year cognitive trajectories among UK population. MethodsThis community-based study enrolled 4,082 postmenopausal women (mean age, 64.2{+/-}10.7 years) with baseline cognition and at least one follow-up assessment from the English Longitudinal Study of Ageing (ELSA) Waves 3-10. Age at menopause was categorized as <40 (premature), 40-49, and [&ge;]50 years (late), with [&ge;]50 years as the reference. Cognitive function was measured by global cognition, which was a composite of three domain-specific tests: semantic fluency, memory, and orientation. Multivariate-adjusted linear mixed models were employed to estimate the longitudinal associations. ResultsCompared with late menopause, menopause at 40-49 years was not associated with lower baseline global cognition or faster long-term decline in global cognition. Premature was associated with lower baseline global cognition ({beta}=-0.218 SD, 95% CI -0.313 to -0.123, p<0.001), with consistent finding across semantic fluency, memory, and orientation tests. However, premature menopause was not significantly related to a faster rate of decline in global cognition ({beta}=-0.010 SD/year, 95% CI -0.022 to 0.002, p=0.112). In domain-specific tests, premature menopause was associated with faster decline in memory test ({beta}=-0.011 SD/year, 95% CI -0.021 to -0.001, p=0.027), while menopause at 40-49 years was associated with faster decline in semantic fluency test ({beta}=-0.007 SD/year, 95% CI -0.013 to -0.001, p=0.015). Surgical menopause and hormone replacement therapy did not modify the association between premature menopause and global cognition. ConclusionPremature menopause was associated with poorer cognitive performance later in life, whereas long-term global cognitive decline was broadly similar across menopause-age groups. These findings suggest that the cognitive impact of premature menopause may be concentrated in earlier postmenopausal years, highlighting the importance of monitoring cognitive change and implementing preventive strategies soon after menopause.