Accelerated epigenetic age and cognitive decline among urban-dwelling adults.

OBJECTIVES: Epigenetic modifications are closely linked with aging, but their relationship with cognition remains equivocal. Given known sex differences in epigenetic aging, we explored sex-specific associations of 3 DNA methylation (DNAm)-based measures of epigenetic age acceleration (EAA) with baseline and longitudinal change in cognitive performance among middle-aged urban adults.
METHODS: We used exploratory data from a subgroup of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study with complete DNA samples and whose baseline ages were >50.0 years (2004-2009) to estimate 3 DNAm EAA measures: (1) universal EAA (AgeAccel); (2) intrinsic EAA (IEAA); and (3) extrinsic EAA (EEAA). Cognitive performance was measured at baseline visit (2004-2009) and first follow-up (2009-2013) with 11 test scores covering global mental status and specific domains such as learning/memory, attention, visuospatial, psychomotor speed, language/verbal, and executive function. A series of mixed-effects regression models were conducted adjusting for covariates and multiple testing (n = 147-156, ∼51% men, k = 1.7-1.9 observations/participant, mean follow-up time ∼4.7 years).
RESULTS: EEAA, a measure of both biological age and immunosenescence, was consistently associated with greater cognitive decline among men on tests of visual memory/visuoconstructive ability (Benton Visual Retention Test: γ11 = 0.0512 ± 0.0176, p = 0.004) and attention/processing speed (Trail-Making Test, part A: γ11 = 0.219 ± 0.080, p = 0.007). AgeAccel and IEAA were not associated with cognitive change in this sample.
CONCLUSIONS: EEAA capturing immune system cell aging was associated with faster decline among men in domains of attention and visual memory. Larger longitudinal studies are needed to replicate our findings.