Cerebral Ischemia Mediates the Effect of Serum Uric Acid on Cognitive Function

BACKGROUND AND PURPOSE: High normal concentrations of serum uric acid (UA) are associated with mild cognitive dysfunction and increased cerebral ischemia as indexed by white matter hyperintensity volumes. We hypothesized that individual differences in white matter hyperintensities mediate the association between UA and mild cognitive dysfunction. METHODS: One hundred eighty community-dwelling adults aged 20 to 96 years completed neuropsychological testing, laboratory blood studies, and a brain MRI scan. RESULTS: Serum UA was associated (P<0.05) with greater white matter hyperintensities and poorer working memory, processing speed, fluency, and verbal memory. Associations remained after controlling for age, sex, race, education, hypertension, diabetes, alcohol abuse, smoking, and body mass. Adding a term for white matter hyperintensity attenuated these associations such that UA no longer predicted cognitive performance. CONCLUSIONS: Severity of cerebral ischemia might mediate the association between UA and cognitive dysfunction. Even mild elevations in UA appear to contribute to structural and functional brain changes.