Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study
PubMed 28754803 · doi:10.1136/annrheumdis-2016-210767
What was done
Researchers evaluated 1,598 community-dwelling older adults (mean age 72.4 years, 38.3% male) from the Three-City Dijon cohort over a median follow-up of 10.1 years (13,357 person-years). They assessed the longitudinal association between baseline serum uric acid (SUA) levels and incident dementia diagnosed by DSM-IV criteria, along with MRI markers of brain aging (white matter hyperintensity volume, lacunes, and hippocampal volume).
What was found
Incident dementia developed in 110 participants (crude incidence rate 8.2 per 1,000 person-years). After multivariable adjustment, individuals in the highest SUA quartile (≥75th percentile) had an increased risk of dementia compared to the lowest quartile (HR 1.79, 95% CI 1.17 to 2.73, p=0.007). The association was stronger for vascular or mixed dementia (HR 3.66, 95% CI 1.29 to 10.41, p=0.015) than for Alzheimer's disease (HR 1.55, 95% CI 0.92 to 2.61, p=0.10). A non-significant trend was observed between high SUA and extensive white matter hyperintensity volume (p=0.10), with no association found for lacunes (p=0.86) or hippocampal volume (p=0.94).
Why it matters
These findings challenge the view that uric acid is neuroprotective against cognitive decline, indicating that high serum uric acid may instead elevate dementia risk, particularly vascular and mixed types.
Limits
The observational design cannot establish causality. The total number of dementia events was modest (n=110), resulting in wide confidence intervals for subtype analyses. In addition, the association with vascular dementia may be confounded or mediated by interim strokes, and findings are from a single cohort of older French adults.
Cited by
- partial A 2018 study following 1,600 Japanese participants for 12 years found that individuals in the highest uric acid group had an 80% increased risk of all-cause dementia, a 55% increased risk of Alzheimer's, and a 166% increased risk of mixed/vascular dementia.