Earlier menopause is associated with both reduced cognitive performance and gray matter volume: a population-based cross-sectional study

BackgroundAge 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 studies investigating cognitive outcomes suggest reduced age-related cognitive performance with earlier menopause. ObjectivesThis study aims to investigate whether earlier age at menopause is associated with reduced cognitive performance and brain structure in later-life in a population-based cohort. To our knowledge, this is one of the only studies examining both cognition and neuroimaging in the same cohort of post-menopausal women, and the first study to formally test whether gray matter volume mediates the relationship between menopause timing and cognitive performance within the same population-based sample. MethodsWe analyzed data from the Cambridge Centre of Neuroscience and Aging, which included 747 postmenopausal women who underwent cognitive testing (Addenbrookes Cognitive Examine Revised, ACE-R). A subset (n=190) 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 gray matter volume, controlling for chronological age. ResultsEarlier menopause was associated with lower cognitive performance, as measured by the ACE-R, with similar associations for fluid intelligence. Structural brain analyses revealed that earlier age at menopause was associated with decreased total gray matter volume (TIV-corrected). No significant interactions were observed between age at menopause and chronological age for any of the outcomes. GMV was a partial mediator between age at menopause and cognitive performance, while controlling for chronological age. ConclusionIn a population-based sample, women with earlier age at 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.