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Disentangling the effects of menopause on cognitive performance: causal framework and findings of the LIFE-Adult-Study

Bonberg, N.; Zuelke, A. E.; Roehr, S.; Luppa, M.; Wirkner, K.; Baber, R.; Schroeter, M.; Villringer, A.; Sacher, J.; Witte, V.; Engel, C.; Loeffler, M.; Riedel-Heller, S. G.; Minnerup, H.

2025-03-06 epidemiology
10.1101/2025.03.06.25323411 medRxiv
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ObjectiveTo investigate the effects of age at natural menopause and reproductive lifespan on cognitive performance using causal reasoning. MethodsWe first identified potential mechanisms linking menopause and cognition focusing on the potential causal role of cumulative estrogen exposure. We then used cross-sectional data from approximately 2,200 postmenopausal women from the population-based LIFE-Adult Study to examine the effect of age at natural menopause and reproductive lifespan, as proxies for cumulative estrogen exposure, on neuropsychological test scores (Trail Making Tests A&B and CERAD Word Fluency Test), considering potential confounding and moderating variables. Results: Assuming that both age at menopause and reproductive lifespan are indicators of cumulative estrogen exposure, the data analysis revealed that women with later age at menopause and longer reproductive lifespan, respectively, performed better on all neuropsychological tests. ConclusionIt is crucial to identify the causal framework when investigating the effects of women specific factors on cognition, especially when it comes to time-dependent effects, as well as complex moderating and mediating factors.

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