When the clock shifts: menopause timing is associated with reduced cognitive performance and gray matter volume in a...

This study investigated whether earlier menopause is associated with reduced later-life cognitive performance and brain structure in a population-based cohort. It is among a few studies examining both cognition and neuroimaging within the same postmenopausal sample, and the first to test whether gray matter volume mediates the relationship between menopause timing and cognitive performance within the same sample.

We analyzed data from the Cambridge Centre of Neuroscience and Aging, including 747 postmenopausal women who underwent cognitive testing. A subset was additionally tested with a fluid intelligence test and structural brain scans. Multiple linear regression models evaluated the association between menopause age, cognitive performance, and gray matter volume, controlling for chronological age, education, depressive symptoms, and physical activity.

Earlier menopause was associated with lower cognitive performance ( t717 =2.2, P =0.028) and fluid intelligence ( t153 =1.59, P =0.026). Structural imaging analyses (n=182) revealed that earlier menopause was associated with decreased total gray matter volume ( t182 =0.152, P =0.024). Exploratory mediation analysis showed that total gray matter volume partially mediated the relationship between age at menopause and cognitive performance ( P =0.006).

In this population-based cohort, earlier menopause was associated with both lower cognitive performance and reduced gray matter volume, suggesting a potential 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 explore potential targeted interventions.