Objectives In patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia.
Methods We assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort). Additionally, we investigated the relation between SUA level and MRI markers of brain ageing (white matter hyperintensity volume (WMHV), lacunes and hippocampal volume).
Results The study sample comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the 13,357 person-years of follow-up (median duration: 10.1 years), dementia developed in 110 participants (crude incidence rate: 8.2/1000 person-years). After multiple adjustments, the multivariate HR with the highest (≥75th percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015) than Alzheimer's disease (HR=1.55 (95% CI 0.92 to 2.61), p=0.10). There was a non-significant trend towards an association between high SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA level and vascular or mixed dementia might be affected by interim strokes.
Conclusions Risk of dementia, especially vascular or mixed dementia, may be increased with high SUA levels in elderly people.
- cardiovascular disease
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Contributors All authors contributed substantially to the conception or design of the work, or the acquisition, analysis or interpretation of data for the work; drafted the work or revised it critically for important intellectual content; gave their final approval of the version to be published; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding The 3-City Study is conducted under a partnership agreement among the Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen–Bordeaux II University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, Caisse Nationale de Solidarité et Longévité (CNSA) and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques.” The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests None declared.
Ethics approval The Ethics Committee of Kremlin-BicÃƒÂªtre University Hospital approved study protocols, and each participant signed a written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data available upon request to the 3C data access committee. Please email requests to: E3C.CoordinatingCenter@gmail.com and E3C.U708@inserm.fr.