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 three DNA methylation-based (DNAm) 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 sub-group of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study with complete DNA samples and whose baseline ages were >50.0y (2004-2009) to estimate three DNAm EAA measures: (A) universal epigenetic age acceleration (AgeAccel); (B) intrinsic epigenetic age acceleration (IEAA) ; and (C) extrinsic epigenetic age acceleration (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, visuo-spatial, psychomotor speed, language/verbal and executive function executive. 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~4.7y). Results. EEAA, a measure of both biological age and immunosenescence, was consistently associated with greater cognitive decline among men on tests of visual memory/visuo-constructive 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.