Sex-Based Differences in the Association of Epigenetic Age Acceleration with Alzheimer's Disease Biomarkers and Cognitive Measures.

Alzheimer's Disease (AD) is a neurodegenerative disorder marked by cognitive and functional decline. Biological sex has been linked to differences in lifetime AD risk, AD-related neuropathology, and the rate of cognitive decline, although the underlying biological mechanisms driving these disparities remain unclear. Epigenetic Age Acceleration-a metric derived from epigenetic aging clocks-has been associated with numerous aging-related conditions such as AD. Although there is promise in using Epigenetic age acceleration as a biomarker for several aging related diseases, the underlying mechanism that aging clocks are actually predicting is not well understood. In this study, we used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to examine how sex influences the relationship between age acceleration and cognitive performance as well as brain volume. Our findings suggest that, although epigenetic age acceleration can predict changes in brain structure, these changes don't appear to be different across sexes. Future research should focus on validating these findings in an external cohort and exploring them longitudinally.