Epigenetic age acceleration and cognitive performance over time in older adults

AbstractINTRODUCTIONThis study investigated whether epigenetic age acceleration (AA) is associated with the change in cognitive function and the risk of incident dementia over 9 years, separately in males and females.METHODSSix epigenetic AA measures, including GrimAge, were estimated in baseline blood samples from 560 Australians aged ≥70 years (50.7% female). Cognitive assessments included global function, episodic memory, executive function, and psychomotor speed. Composite cognitive scores were also generated. Dementia (Diagnostic and Statistical Manual for Mental Disorders – IV [DSM‐IV] criteria) was adjudicated by international experts.RESULTSAssociations between epigenetic AA and cognitive performance over‐time varied by sex. In females only, GrimAA/Grim2AA was associated with worse delayed recall, composite cognition, and composite memory (adjusted‐beta ranged from –0.1372 to –0.2034). In males only, GrimAA/Grim2AA was associated with slower processing speed (adjusted‐beta, –0.3049) and increased dementia risk (adjusted hazard ratios [HRs], 1.78 and 2.00, respectively).DISCUSSIONEpigenetic AA is associated with cognitive deterioration in later life but with evidence of sex‐specific associations.Highlights Epigenetic age acceleration was associated with cognitive deterioration over time. However, these associations differed by sex. In females, accelerated GrimAge appeared to be a better marker of decline in memory. In males, accelerated GrimAge was associated with slower processing speed over time. Association between accelerated GrimAge and dementia risk was found only in males.