Exploring Epigenetic Age Acceleration and Cognitive Change in Middle Adulthood

Background and Objectives: Positive epigenetic age acceleration, in which a person’s biological age is older than their chronological age, is associated with worse cognitive performance. Most findings, however, rely on cross-sectional lab-administered measures of cognition or longitudinal average scores that collapse the time-ordered effects of practice. The present study leveraged a measurement burst dataset to examine distinct features of cognitive performance (i.e., peak performance, change in peak performance, intraindividual variability, forgetting, retest-related gains), and explored whether individual differences in these features can be predicted by age acceleration and chronological age. Research Design and Methods: In a sample of 139 adults aged 25-65, estimates of baseline age acceleration were derived from DNA methylation (Horvath1, Horvath2, Hannum, PhenoAge, GrimAge, DunedinPACE). Across four annual high-frequency assessment bursts, processing speed was assessed via a Symbol Search task and working memory was evaluated via a N-Back task.Results: Using Bayesian Double Exponential Models (BDEMs) separately testing different DNA methylation age acceleration as predictors of cognitive performance indices, we found in both tasks that baseline peak performance was lower for individuals with greater age acceleration and those who were chronologically older. Individuals with greater age acceleration showed greater retest-related gains within and across bursts. Neither age acceleration or chronological age predicted differences in longitudinal change. Interestingly, individuals with greater age acceleration and older chronological age showed more intraindividual variability in symbol search performance. Finally, greater chronological age (but not age acceleration) was linked with more forgetting between bursts in both tasks.Discussion and Implications: Rather than relying on level, these findings underscore the value of multidimensional indices of cognitive performance. Importantly, even in a sample spanning young adulthood through early old age, such indices may provide more information regarding the nature of longitudinal patterns in cognition associated with chronological or biological aging.