Associations of serum uric acid with incident dementia and cognitive decline in the ARIC-NCS cohort

Introduction: Elevated serum uric acid (SUA) is associated with cardiovascular risk factors, which often contribute to dementia and dementia-like morbidity, yet several cross-sectional studies have shown protective associations with cognition, which would be consistent with other work showing benefits of elevated SUA through its antioxidant properties. Methods: We studied 11,169 participants free of dementia and cardiovascular disease from the Atherosclerosis Risk in Communities (ARIC) cohort. SUA was measured in blood samples collected in 1990-92, baseline for this study (age range 47-70 years). Incident dementia was ascertained based on clinical assessments in 2011-13 and 2016-17, surveillance based on dementia screeners conducted over telephone interviews, hospitalization discharge codes, and death certificates. Cognitive function was assessed up to four times between 1990 and 92 and 2016-17. We estimated the association of SUA, categorized into quartiles, with incidence of dementia using Cox regression models adjusting for potential confounders. The association between cognitive decline and SUA was assessed using generalized estimating equations. Results: Over a median follow-up period of 24.1 years, 2005 cases of dementia were identified. High baseline SUA was associated with incident dementia (HR, 1.29; 95% CI, 1.12, 1.47) when adjusted for sociodemographic variables. However, after further adjustment including cardiovascular risk factors, this relationship disappeared (HR, 1.03; 95% CI, 0.88, 1.21). Elevated baseline SUA was associated with faster cognitive decline even after further adjustment (25-year global z-score difference, -0.149; 95% CI, -0.246, -0.052). Conclusion: Higher levels of mid-life SUA were associated with faster cognitive decline, but not necessarily with higher risk of dementia.