Earlier menopause is associated with both reduced cognitive performance and gray matter volume: a population-based cross-sectional study
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Background
Age at menopause varies widely across women, yet little is known about how this relates to long-term behavioral and brain-structural changes. Previous research has focused primarily on the menopausal transition itself, and the few studies investigating cognitive outcomes suggest reduced age-related cognitive performance with earlier menopause.
Objectives
This study aims to investigate whether earlier menopause onset is associated with reduced cognitive performance and brain structure in later-life, in the same cohort of postmenopausal women.
Methods
We analyzed data from the Cambridge Centre of Neuroscience and Aging, which included 747 postmenopausal women who underwent cognitive testing (Addenbrooke’s Cognitive Examination Revised, ACE-R). A subset (n=188) was additionally tested with a fluid intelligence test and underwent structural brain scans to measure gray and white matter volume (GMV and WMV). Multiple linear regression models were used to evaluate the association between menopause age and cognitive performance, as well as grey matter volume, controlling for chronological age.
Results
Earlier menopause onset was associated with lower cognitive performance, as measured by the ACE-R ( t (719)=2.81, p =0.005). Similar results were found for fluid intelligence ( t (146) = 3.116, p =0.002). Structural brain analyses showed that a reduction of one year at the age of menopause onset was associated with a reduction of 2370mm 3 in total grey matter volume ( t (182)=3.37, p =0.001). No significant interactions were observed between menopause onset age and chronological age for any of the outcomes. GMV was a partial mediator between age at menopause onset and cognitive performance, while controlling for age.
Conclusion
Women with earlier menopause show both reduced cognitive performance and lower GMV, suggesting that GMV reduction may be one mechanism linking earlier menopause to cognitive decline. However, the cross-sectional nature of this study prevents causal conclusions, and longitudinal research is needed to establish causal links and to explore potential targeted interventions.
