GENDER-SPECIFIC EFFECTS OF IL-6 AND DECLINES IN PROCESSING SPEED AND EXECUTIVE FUNCTIONING IN OLDER ADULTS

Abstract Elevated peripheral inflammatory markers among older adults associate 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 differences vs. fluctuations in inflammation. Participants (N = 235) were older adults (Mage = 75.1, range = 60-92) from a longitudinal study of neuropsychological assessments and blood draws every six months across up to 12 years. Systemic inflammation was operationalized as serum IL-6. The Trail Making Test provided assessment of psychomotor processing speed (A) and executive functioning (B and B-A). Multilevel models tested associations between cognition and inflammation and moderation by gender. Higher stable differences and fluctuations over time in IL-6 were significantly associated with slower TMT-A performance for women and men (between-person: g = -.06, p =.04; within-person: g = -.02, p =.049). Higher IL-6 was more strongly associated with slower TMT-B and B-A performance for men (TMT-B: g =.006, p =.02; TMT-B-A: g =.008, p =.01). Older participants demonstrated slower TMT-A performance at higher IL-6 (g =.026, p =.01). Women experience higher rates of Alzheimer’s disease diagnosis and faster age-related cognitive decline, suggesting gender-specific factors related to cognition yet to be uncovered. In the present study, executive function was sensitive to changes in systemic inflammation in a gender-specific way. Gender-specific differences in neurological aging remains a critical target for future intervention research aimed at addressing preclinical AD and accelerated aging.