Association between higher serum uric acid levels and cognitive function: a systematic review and meta-analysis

Serum uric acid (SUA) levels may be associated with cognitive function, but findings have been inconsistent, potentially varying by cognitive domain and sex. We aimed to determine the association of SUA and different domains of cognitive function.

Five electronic databases were searched to identify relevant peer-reviewed articles. Studies investigating the association between SUA levels and cognitive function were included. Standardized mean difference (SMD) was calculated, and separate meta-analyses were conducted for each of the domains. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Between-study heterogeneity was investigated through subgroup analysis and a meta-regression model using study-level covariates.

Ten prospective cohort and 16 cross-sectional studies were eligible for inclusion, but only a subset of these studies was included in each meta-analysis. Pooled estimates from cross-sectional studies showed that higher SUA levels were significantly associated with better global cognition (n = 6, SMD = 2.27, 95% CI, 1.18-3.35), and learning and memory (n = 4, SMD = 1.49, 95% CI, 1.12-1.87). Sensitivity analysis, excluding the study conducted on amyotrophic lateral sclerosis patients, resulted in better performance estimates for executive function (n = 4, SMD = 0.51, 95% CI, 0.47-0.55) and language (n = 2, SMD = 0.75, 95% CI, 0.71-0.79). The pooled result from 2 prospective cohort studies found a positive relationship between SUA levels and attention (SMD = 0.22, 95% CI, 0.07-0.36). Serum uric acid levels were associated with executive function and learning and memory in males, and with language in females.

Higher SUA levels were associated with better global cognitive performance executive function, learning and memory, attention and language. These findings highlight low SUA levels as a potentially useful biomarker for cognitive decline.