Epigenetic age acceleration is related to cognition and cognitive decline in the Elderly: Results of the Austrian Stroke Prevention Study

Abstract

Epigenetic clocks, an estimate of biological age based on DNA methylation (DNAmAge) are gaining prominence as potential markers of brain ageing. However, consensus is lacking as the repertoire of DNAmAges expands, particularly concerning their ability to predict age-related cognitive changes. In our cohort of 785 elderly, we examined 11 DNAmAges, evaluating their associations with brain ageing in cross-sectional and longitudinal settings. Our results highlighted DNAmAges as strong predictors of cognitive change compared to baseline cognition, albeit varying performance across cognitive domains. DunedinPACE excelled in predicting baseline cognition, while Zhangs clocks and principal component-based PhenoAge (PCPheno) performed best in predicting cognitive decline. DNAmAges elucidated substantial cognitive variability, matching or surpassing the predictive power of vascular risk factors and ApoE4 genotypes. Notably, in ApoE4 carriers, Zhangs clock and PCPheno exhibited significantly larger effects, explaining over five times the variability in memory decline compared to non-carriers.