High serum uric acid levels may increase risk for dementia in elderly individuals, according to findings from the Three-City Dijon Study (3C-Dijon), a French population-based cohort investigation recently published in the Annals of the Rheumatic Diseases. This association was particularly strong between elevated serum uric acid and vascular or mixed dementia subtypes.
Although there is conflicting evidence regarding the link between serum uric acid and dementia onset, some studies have indicated that serum uric acid is neuroprotective. This has raised concerns about the neurodegenerative implications of low serum uric acid levels, especially as a result of urate-lowering therapies used to combat hyperuricemia and gout. Researchers of 3C-Dijon sought to elucidate the effect of serum uric acid levels on the incidence of dementia.
A total of 1598 participants (mean age, 72.4 years; 61.7% women) were initially assessed between 1999 and 2001, and then followed for 12 years, with 6 follow-up visits every 2 years. Throughout the study period, 110 participants were diagnosed with dementia, yielding a crude incidence rate of 8.2/1000 person-years. Older age (P <.0001) and apolipoprotein E carriage (P <.0001) were associated with incident dementia.
After multiple adjustments, the hazard ratio (HR) for all-cause dementia incidence in the highest quartile vs lowest quartile of serum uric acid levels was 1.79 (95% CI, 1.17-2.73; P =.007), indicating a correlation between higher serum uric acid levels and dementia. Vascular or mixed dementia subtypes demonstrated a stronger association with elevated serum uric acid (HR, 3.66; 95% CI, 1.29-10.41; P =.015) than Alzheimer’s disease (HR, 1.55; 95% CI, 0.92-2.61; P =.10).
A nonsignificant trend was demonstrated between high serum uric acid and increased white matter hyperintensity volume (P =.10), but neither hippocampal volume (P =.94) nor lacunes (P =.86) were associated with elevated serum uric acid levels.
The authors described several study strengths, including large size with extensive follow-up, thorough dementia diagnostic procedures with evaluation of subtypes, parallel assessment of MRI brain markers, rigorous patient screening for multiple factors, use of sensitivity analyses, and an avoidance of sex bias via use of separate serum uric acid cutoffs.
Researchers also identified several limitations, including lack of perfect representation of the larger French population, possibly limiting generalizability; use of an elderly sample that may not accurately reflect lifelong serum uric acid levels; use of a single serum uric acid measurement that cannot account for time-based serum uric acid effects; and the potential for survival and selection biases.
Despite previous reports of a connection between decreased serum uric acid and neurodegenerative diseases, the 3C-Dijon results indicate an increased risk for dementia with higher serum uric acid levels in elderly patients.