Executive function and soluble urokinase-type plasminogen activator receptor (suPAR): a longitudinal study of midlife adults

Executive function (EF) declines with age. Declines in EF are associated with adverse outcomes, but there is substantial inter-individual variability in rate and magnitude of decline. Evidence suggests that systemic inflammation may contribute to declines in EF. Extant studies are largely cross-sectional and examine markers of inflammation that are not specific to the immune system and influenced by acute contemporaneous factors. We examined a newer marker of chronic inflammation, soluble urokinase Plasminogen Activator Receptor (suPAR) alongside more traditional markers, IL-6 and CRP. We hypothesized that higher baseline and greater increases in suPAR across an 8-19 (median 17) year period of midlife would associate with larger age-related declines in EF. Data were drawn from the Adult Health and Behavior (AHAB) study (n=599). Participants (55.5% female, 86.2% white, mean age 45 years at W1 and 60 years at W2) completed a neuropsychological battery and blood draw at both waves. EF was comprised of the Trail Making Test, the STROOP Test, and Matrix Reasoning. Univariate and Bivariate Latent change score models (LCSM) examined whether baseline and change in circulating levels of inflammatory mediators were associated with change in EF from W1 to W2. Baseline inflammation was not associated with change in EF. Increases in suPAR were significantly related to concomitant declines in EF (= -0.315; p <.05). No similar effects were observed for IL6 or CRP. Further research should examine suPAR as potential marker of chronic systemic inflammation and its relationship to cognitive aging.