Older adults with high serum uric acid (SUA) levels might be at increased risk of developing vascular or mixed dementia, according to a longitudinal study recently published in the Annals of Rheumatic Diseases.1 The study adds to the body of evidence showing an association between dementia and high SUA levels, despite some evidence suggesting that uric acid (UA) has antioxidant properties and is neuroprotective.2-4
“Most studies that investigated the link between SUA level and dementia were cross-sectional, with risk of bias…and longitudinal studies are scarce. Thus, more longitudinal population-based cohort studies are needed to better unravel the complex link between UA and cognitive impairment,” the investigators wrote.
The study is an ancillary study to the Three-City Study, a population-based longitudinal study assessing the relationship between vascular diseases and dementia in individuals aged ≥65 years (n=9294) randomly selected from the electoral rolls of 3 French cities: Bordeaux (n=2104), Dijon (n=4931), and Montpellier (n=2259).5 The current study included 1598 patients from the Dijon cohort who had a baseline assessment of SUA level (mean SUA at baseline, 273.7±70.4 µmol/L), no clinical diagnosis of dementia at baseline, a Mini-Mental State Examination score of >24, and at least 1 follow-up visit.
The study’s primary endpoint was dementia risk (all-cause, Alzheimer’s disease, vascular, or mixed) in relation to SUA level. Because SUA levels are consistently lower in women than in men, the investigators used SUA quartiles they generated using sex-dependent thresholds.
Compared with individuals in the lowest quartile of SUA levels (<260 μmol/L for men and <209 μmol/L for women), those in the highest quartile (≥345 μmol/L for men and ≥292 μmol/L for women) were at significantly increased risk for dementia (hazard ratio [HR], 1.90; 95% confidence interval, 1.10-3.29; P =.008). This association persisted even after adjusting for various confounders, including cardiovascular risk factors, use of nonsteroidal anti-inflammatory drugs and other agents affecting SUA levels, and presence of inflammatory markers. The association between SUA and dementia was strongest for vascular or mixed-type dementia (HR, 6.41; 95% confidence interval, 1.20–34.29; P =.022) vs Alzheimer’s disease (HR, 1.89; 95% confidence interval, 0.94-3.83; P =.06).
As secondary endpoints, the researchers examined the relationship between SUA levels and various markers of brain aging detected on magnetic resonance imaging, including white matter hyperintensity volume, lacunes, and hippocampal volume. No associations between SUA levels and these markers were found.
Summary & Clinical Applicability
Older adults with high SUA levels might be at increased risk for dementia, particularly vascular or mixed type. Other prospective large-scale studies are needed to confirm these findings; however, until such data become available, clinicians treating patients with gout should continue to follow the American College of Rheumatology’s SUA-lowering recommendations.6
Limitations & Disclosures
Limitations of the study include small sample size restricted to a single city in France, older age of the study population, and potential of survival bias (ie, those with high SUA levels may have died from cardiovascular disease before the age limit for enrollment in the Three-City Study was lowered to 65 years). In addition, the findings were based on a single measure of SUA, preventing evaluation of the time-varying effects of SUA, a factor that might have a more pronounced effect on dementia risk.
The Three-City Study was funded by various academic and commercial organizations, including a partnership agreement with Sanofi-Aventis; however, the funders were reported to have no role in the study design, data collection and analysis, decision to publish, or manuscript preparation.
- Latourte A, Soumaré A, Bardin T, Perez-Ruiz F, Debette S, Richette P. Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study [published online July 28, 2017]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2016-210767
- Khan AA, Quinn TJ, Hewitt J, et al. Serum uric acid level and association with cognitive impairment and dementia: systematic review and meta-analysis. Age. 2016;38(1):16.
- Maxwell SR, Thomason H, Sandler D, et al. Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus. Eur J Clin Invest. 1997;27(6):484-490.
- Shen L, Ji HF. Low uric acid levels in patients with Parkinson’s disease: evidence from meta-analysis. BMJ Open. 2013;3(11):e003620.
- The Three-City Study/Étude des 3 cités. http://www.three-city-study.com. Accessed August 10, 2017.
- Khanna D, FitzGerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout part i: systematic non-pharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64(10):1431-1446.