medwireNews: Older people with higher levels of serum uric acid (SUA) may have a greater risk for dementia than those with lower levels, results of a longitudinal study suggest.
“Hyperuricemia is a prerequisite for gout and might be a risk factor for cardiovascular and kidney diseases,” say Pascal Richette (Hôpital Lariboisière, Paris, France) and fellow researchers.
However, they explain that “maintaining too low SUA levels is [also] a concern,” with cross-sectional studies providing conflicting evidence on the association between SUA and dementia.
In an analysis of 1598 community-dwelling older people aged at least 65 years who were not receiving urate-lowering treatments (ULTs) in the Three-City Dijon Study, the team found that 110 participants developed dementia over a median 10.1 years of follow-up, including 76 patients with Alzheimer’s disease and 20 with vascular or mixed dementia.
Individuals with SUA levels in the highest quartile (≥345 μmol/L for men and ≥292 μmol/L for women) were approximately twice as likely to develop dementia as those with SUA levels in the lowest quartile (<260 μmol/L for men and <209 μmol/L for women), with a hazard ratio (HR) of 2.21 after adjustment for factors including demographics, body mass index, comorbidities, and medication use, and a HR of 2.43 after further adjustment for C-reactive protein (CRP) and interleukin (IL)-6 levels.
And SUA levels were more strongly associated with vascular or mixed dementia than with Alzheimer’s disease, with a significant HR for the highest versus lowest SUA quartile of 6.41 for vascular or mixed dementia, and a nonsignificant HR of 1.89 for Alzheimer’s disease in the fully adjusted analysis.
The team also identified a “non-significant trend towards an association” between high SUA levels and white matter hyperintensity volume (WMHV), a magnetic resonance imaging marker of small vessel disease. This trend became statistically significant when participants receiving ULT were included in the analysis.
“Participants receiving ULT are likely patients with gout (ie, with the highest SUA levels), and may thus be particularly exposed to cerebrovascular disease,” say the authors, which “may explain why the association between SUA and WMHV was not significant” when participants taking SUA were excluded from the analysis.
“[C]onsistently, we found a higher prevalence of cardiovascular comorbidities in participants taking ULT than in the main sample,” they add.
The association between high SUA levels and WMHV was not significant, however, in the fully adjusted model taking CRP and IL-6 levels into account.
Richette and colleagues caution that the effects of elevated SUA levels over time could not be assessed in their study as only baseline measurements were available, and note that SUA levels in older people may be modified by unmeasured confounders, including initiation of treatment and age-related chronic diseases.
They therefore conclude in the Annals of the Rheumatic Diseases: “These results require confirmation in other prospective large-scale studies including younger individuals with long follow-up duration and ideally repeated measurements of SUA.”
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