Higher interleukin-6 (IL-6) is associated with decline in psychomotor processing speed but not executive functioning...

Elevated peripheral inflammatory markers among older adults are associated with cognitive decline, particularly for women, for whom cognitive decline is more prevalent and rapid. Few prospective studies have examined gender-specific associations between inflammation and cognitive decline or examined stable, mean differences (i.e., between-person effects) versus fluctuations (i.e., within-person effects) in inflammation.

Participants (N = 235) were older adults (Mage= 75.1, range = 60-92) from a longitudinal study that included neuropsychological assessments and blood draws every six months for up to 12 years. Systemic inflammation was operationalized as serum interleukin-6 (IL-6). The Trail Making Test measured psychomotor processing speed (TMT-A), task-switching (TMT-B), and executive functioning (TMT-B-TMT-A). Multilevel models tested associations between cognition and inflammation and moderation by gender. Models controlled for relevant covariates (e.g., age, gender, education, body mass index, cardiovascular medication count).

Higher mean IL-6 was associated with slower TMT-A performance for women (γ = .036, p = .04) but not men (γ = -.01, p = .45). Higher mean IL-6 was associated with slower TMT-B performance (γ = .036, p = .02), but not after covariate adjustment (γ = .016, p = .28) and there was no significant moderation by gender. There were no significant associations between within-person IL-6 and any outcome, between- or within--person IL-6 and TMT B-A performance, or any 3-way interactions between gender, IL-6, and study wave on any outcome.

Psychomotor speed, but not executive function, was sensitive to changes in systemic inflammation in a gender-specific way. -Gender-specific differences in neurological aging remain a fruitful direction and critical target for future intervention research aimed at addressing preclinical Alzheimer's disease and accelerated aging.