Moderate increase of serum uric acid within a normal range is associated with improved cognitive function in a non-normotensive population: A nationally representative cohort study

BACKGROUND: Associations between serum uric acid (SUA) and changes in cognitive function are understudied in non-normotensive populations, and many previous studies only considered the baseline SUA at a single time point. We aimed to examine the effects of baseline SUA and 4-year changes in SUA on cognitive changes in the non-normotensive population. MATERIALS AND METHODS: In the China Health and Retirement Longitudinal Study (CHARLS), cognitive function was measured based on executive function and episodic memory in four visits (years: 2011, 2013, 2015, and 2018). We identified two study cohorts from CHARLS. The first cohort included 3,905 non-normotensive participants. Group-based single-trajectory and multi-trajectory models were applied to identify 7-year cognitive trajectories. Adjusted ordinal logistics models were performed to assess the association between baseline SUA and 7-year cognitive trajectories, and subgroup analyses were conducted according to the presence of hyperuricemia or SUA levels. The second cohort included 2,077 eligible participants. Multiple linear regression was used to explore the effect of a 4-year change in SUA on cognitive change during the subsequent 3-year follow-up. RESULTS: Four distinct single-trajectories of global cognitive performance and four multi-trajectories of executive function and episodic memory were identified. Higher baseline SUA levels were significantly associated with more favorable cognitive single-trajectories (OR(Q4 vs). (Q1): 0.755; 95% CI: 0.643, 0.900) and multi-trajectories (OR(Q4 vs). (Q1): 0.784; 95% CI: 0.659, 0.933). Subgroup analyses revealed that the protective effect of SUA was significant in the non-hyperuricemia groups or the low-level SUA groups. Additionally, changes in SUA could influence future cognitive changes. Compared with non-hyperuricemia participants with elevated SUA, non-hyperuricemia participants with decreased SUA and patients with persistent hyperuricemia had a higher risk for cognitive decline. Furthermore, only the Q3 group of changes in SUA could enhance global cognitive function compared with the Q1 group (β: 0.449; 95% CI: 0.073, 0.826). CONCLUSION: Our study indicates that the maintenance of normal SUA levels and a moderate increase of SUA were advantageous in improving cognitive function or trajectories in a non-normotensive population. Conversely, SUA may impair cognitive function in patients with persistent hyperuricemia.