Possible Effect of Allopurinol and Risk of Dementia: An Updated Meta-Analysis
Main Article Content
Keywords
allopurinol, dementia, gout, xanthine oxidase, uric acid, cognitive function
Abstract
Background: Allopurinol is widely prescribed for the management of gout and hyperuricemia through inhibition of xanthine oxidase. While uric acid possesses antioxidant properties, xanthine oxidase activity contributes to oxidative stress, raising uncertainty regarding the long-term cognitive effects of allopurinol therapy. The association between chronic allopurinol use and dementia risk remains unclear. This updated meta-analysis aimed to evaluate the association between long-term allopurinol exposure and the risk of incident dementia in patients with gout or hyperuricemia. Methods: This systematic review and meta-analysis was conducted and reported in line with PRISMA reporting principles. PubMed, MEDLINE, and the Cochrane Library were systematically searched for observational studies published between January 2015 and August 2024. Study quality was assessed using the Newcastle–Ottawa Scale. Adjusted hazard ratios (HRs) derived from time-to-event analyses were prespecified as the primary effect measure, reflecting longitudinal dementia risk, while adjusted odds ratios (ORs) were analyzed separately as a secondary outcome. Meta-analyses were performed using a random-effects model in Review Manager (RevMan) version 5.4. Results: Nine studies met the inclusion criteria, comprising cohort, case-control, and nested case-control designs. In the primary HR-based meta-analysis, long-term allopurinol use was not associated with an increased risk of dementia, with substantial heterogeneity observed. Sensitivity analyses excluding one influential cohort study demonstrated a statistically significant reduction in incident dementia, with reduced heterogeneity. Across individual studies, most effect estimates were below unity, suggesting a neutral-to-potentially protective association. OR-based analyses were limited in number and showed no consistent association. Conclusion: Current evidence indicates that long-term allopurinol therapy is associated with a reduced incidence of dementia in populations, as suggested by sensitivity analyses. These findings support the cognitive safety of allopurinol in routine clinical practice and demonstrate the value of pharmacist-led medication review and longitudinal monitoring. Further well-designed prospective studies are warranted to clarify causality and identify subgroups most likely to benefit.
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