The Effect of Hyperuricemia on Cognitive Impairment: A Cohort Study and Systematic Review

Hyperuricemia may influence cognitive function, but current evidence remains inconsistent. This study examined the association between hyperuricemia/gout and cognitive impairment through a prospective cohort study and a systematic review of cohort studies.

Data from 1959 Taiwan Biobank participants aged ≥60 years without mild cognitive impairment (MCI) or dementia at baseline were analyzed over a mean follow-up duration of 4.47 years (2012-2021). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Participants were classified by changes in serum uric acid status from baseline to follow-up, and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For the systematic review, cohort studies published up to March 2026 were identified from eight databases.

During follow-up, 1013 participants developed incident MCI and 132 developed dementia. Compared with participants who maintained normal serum uric acid levels, those who developed hyperuricemia during follow-up had a significantly lower MCI risk (HR = 0.72, 95% CI = 0.57-0.90), as did those with persistent hyperuricemia (HR = 0.78, 95% CI = 0.64-0.95). No significant association was observed for dementia. The systematic review of five prospective cohort studies comprising 2,261,704 participants showed inconsistent findings with considerable heterogeneity (I² = 96.7%).

Rising serum uric acid levels were associated with lower MCI risk, but not dementia. These findings should not be interpreted as support for intentionally increasing serum uric acid levels or withholding urate-lowering therapy. Further long-term studies are needed.