Serum Uric Acid Levels and Risk of Cognitive Impairment: Dose-Response Meta-Analysis of Prospective Cohort Studies

Purpose Studying the effects of uric acid levels on cognitive function and quantifying the dose-response relationship. Methods Based on PubMed and Embase search terms, we identified prospective cohort studies that included blood uric acid as a risk factor and cognitive impairment as a result up to September 2022. We extracted pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results Nine reports (including 488,915 participants and 5516 cognitive impairment cases) with median follow-up of 8.8-22 years were eligible for analyses. Compared with lowest category of blood uric acid concentration, the combined RR of cognitive impairment events in the highest classification was 0.81 (95% CI: 0.70-0.92, P < 0.001). Dose-response analysis of eight reports (including 484,297 participants and 5059 cognitive impairment cases) showed that there was no evidence of a curvilinear relationship between blood uric acid levels and cognitive impairment (P = 0.51 for nonlinear relationship). The summary RR of cognitive impairment for an increase of 1 mg/dL blood uric acid level was 0.98 (95% CI: 0.95-1.00; linear trend P = 0.07, I-2 = 67.1%, heterogeneity P < 0.05). There was also a linear negative association between blood uric acid levels and cognitive impairment risk in the male subgroup analysis (RR = 0.97, 95% CI: 0.95-0.99, P < 0.05). Conclusion Levels of blood uric acid are not related to risk of cognitive impairment. A subgroup analysis shows that the rise in blood uric acid levels in the male population is related to a decreased risk of cognitive impairment. These results need to be confirmed by further studies.