Serum Uric Acid as a Biomarker of Cognitive and Functional Decline in Late Life

Johns Hopkins University, Baltimore MD

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Abstract

DESCRIPTION (provided by applicant): Uric acid is rapidly gaining attention because of its seemingly contradictory properties in relation to brain function. In our prior cross-sectional, observational studies of community-dwelling adults, we have demonstrated that mildly elevated-- but still normal-- levels of serum uric acid are associated with significantly poorer cognitive performance and with greater cerebral ischemic burden, even after controlling for age, sex, race, education, diabetes, hypertension, smoking, and alcohol abuse. We have also demonstrated that individual differences in cerebral ischemia mediate the association between uric acid and mild cognitive dysfunction. Taken together, our results support the notion that even mild elevations of serum uric acid are associated with structural and functional brain changes, specifically involving the development of ischemic injury. These findings are interesting and suggest that a clinical trial may be warranted to determine whether uric acid lowering medications prevent or reverse mild cognitive dysfunction in elderly adults with high normal serum uric acid. However, the sample on which these findings were based was relatively small and the relationships were strictly cross-sectional. Therefore, the goal of this pilot project is to replicate these findings in a larger cross-sectional sample and extend our findings by determining whether high normal concentrations of serum uric acid are associated with mild cognitive dysfunction and adaptive functioning longitudinally. We are also seeking to determine whether any observed associations between uric and adaptive functioning are mediated by declines in cognition. To achieve these goals, we have applied for and been granted permission to analyze data from the Women's Health and Aging Study II (WHAS II), a prospective study of healthy elderly women. Participants of the WHAS II underwent serial physical examinations, blood draws (including serum uric acid), cognitive testing, and assessments of adaptive functioning. Should the findings from this investigation indicate that high normal serum uric acid increases the risk of mild cognitive dysfunction longitudinally, after controlling for other health, cardiovascular, and demographic variables it, this would provide powerful evidence further justifying the need for a clinical trial aimed at reducing serum uric acid production in elderly adults with mildly elevated uric acid. PUBLIC HEALTH RELEVANCE: The goal of this pilot project is to replicate and expand on our previous cross-sectional findings relating elevations in serum uric acid to mild cognitive dysfunction in elderly adults by examining both cross-sectional and longitudinal data from the Women's Health and Aging Study-II (WHAS-II). Should the findings from this investigation indicate that high normal serum uric acid increases the risk of mild cognitive dysfunction longitudinally, this would provide powerful evidence further justifying the need for a clinical trial aimed at reducing serum uric acid production in elderly adults with mildly elevated uric acid.