Epigenetic age acceleration and cognitive performance over time in older adults

INTRODUCTION: This 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. METHODS: Six 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. RESULTS: Associations 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). DISCUSSION: Epigenetic 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.