High Uric Acid Levels Linked to Dementia

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Key points
• High levels of serum uric acid are associated with increased risk of vascular or mixed dementia in elderly patients with gout.

• There appears to be a decreased risk of Alzheimer disease with nonsteroidal anti-inflammatory drug (NSAID) use.

• NSAID use did not reduce the incidence of overall dementia.

• The effect of urate-lowering therapy on dementia remains unclear.

Background
Decreasing serum uric acid is the mainstay of therapy for gout. Elevated serum uric acid is thought to contribute to the risk of cardiovascular and kidney disease.

Augustin Latourte and colleagues at multiple international centers point out that while reducing serum uric acid in gout is important, some evidence exists that uric acid has neuroprotective and antioxidant properties that may mitigate neurodegenerative diseases.¹

While the results of studies into serum uric acid levels and cognitive impairment have been conflicting, recent evidence suggests a preventive effect of serum uric acid on Alzheimer disease. The authors sought to determine the risk of incident dementia and brain MRI features conferred by serum uric acid levels in older adults. They recently presented their findings in the Annals of the Rheumatic Diseases.

The study
The authors conducted a French population-based cohort study that included 1598 adults 65 years of age or older. All subjects were screened for serum uric acid levels, and 1924 MRI scans were performed at baseline. The subjects were followed for 12 years. The primary outcome was incident dementia.

The results
• Higher serum uric acid levels were associated with older age, prior cardiovascular disease, and traditional cardiovascular risk factors.

• The highest risk of dementia occurred with the highest quartile of serum uric acid levels (≥ 345 μmol/L for men and ≥ 292 μmol/L for women) with the lowest risk in the lowest quartile (< 260 μmol/L for men; < 209 μmol/L for women) (hazard ratio [HR] = 1.90 [95% CI, 1.10 to 3.29]; P = .008).

• The link between serum uric acid levels and dementia was strongest with vascular or mixed dementia (HR = 6.41 [95% CI, 1.20 to 34.29]; P = .022) vs Alzheimer disease (HR = 1.89 [95% CI, 0.94 to 3.83], P = .06).

• There was no association between serum uric acid levels and MRI evidence of cerebrovascular disease or hippocampal volume (P = .94).

Implications for clinicians
• It appears that higher serum uric acid levels do not confer a neuroprotective benefit when it comes to vascular or mixed dementia.

• Monitor serum uric acid levels in aging patients and consider them to be at higher risk for dementia if levels are elevated.

• Through reduction in inflammation, NSAIDs may reduce the risk of Alzheimer dementia but not the overall risk of dementia.

• These results should be interpreted cautiously as the authors point out more study is needed.

References:

1. Latourte A, Soumare A, Bardin T, et al. Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study. Ann Rheum Dis. 2018;77:328-335. doi:10.1136/annrheumdis-2016-210767