The Association Between Serum Uric Acid and Cognitive Function Among Middle-Aged and Older Adults Without Hyperuricemia: The Mediating Role of Depressive Symptoms

Background: The association between serum uric acid (SUA) and cognitive function remains unclear, especially among individuals without hyperuricemia. We examined the cross-sectional and longitudinal bidirectional associations between SUA and cognition, as well as the mediating effect of depressive symptoms among Chinese adults.Methods: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). SUA (continuous) and cognitive function (based on mental intactness and episodic memory) were measured at Wave 1 and Wave 3. Depressive symptoms (Center for Epidemiologic Studies Depression scale) were assessed at Wave 1. Bivariate latent change score models and mediation analysis were used to investigate these possible associations.Results: A total of 6 236 participants free of hyperuricemia (aged 58.3 +/- 8.5 years) were included. After controlling for potential confounders, the SUA level was associated with cognition at baseline (standardized r = 0.042; p = .001). Higher baseline SUA level was associated with slower subsequent cognitive decline (standardized beta = 0.026; p = .027), whereas baseline cognition was not significantly associated with subsequent change in SUA (standardized beta = 0.003; p = .817). In mediation analysis, baseline SUA was indirectly associated with subsequent cognition via baseline depressive symptoms (mediation effect 13.3%; p < .001).Conclusions: Higher baseline SUA level is associated with better baseline cognition and less subsequent cognitive decline among Chinese adults without hyperuricemia. Baseline depressive symptoms may partially mediate the association between baseline SUA and later cognition. Continued research is warranted to verify these findings and elucidate the causality and underlying mechanisms.