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Serum uric acid and brain ischemia in normal elderly adults

From the Departments of Psychiatry and Behavioral Sciences (D.J.S., A.B.I., T.D.V., G.D.P.), Radiology and Radiological Sciences (D.J.S., M.K.), and Neurology (B.G., H.A.J.), Johns Hopkins University School of Medicine, Baltimore, MD, and Olin Neuropsychiatry Research Center (G.D.P.), Hartford Hospital/Institute of Living, and Department of Psychiatry (G.D.P.), Yale University School of Medicine, New Haven, CT.

Address correspondence and reprint requests to Dr Schretlen, Johns Hopkins Hospital, 600 N. Wolfe St., Meyer 218, Baltimore, MD 21287-7218

Background: Uric acid (UA) has antioxidant properties yet when elevated is associated with vascular disease and stroke. Further, even high normal UA is associated with increased risk of mild cognitive dysfunction in elderly adults.

Method: In this cross-sectional, observational study, we examined the relationship between serum UA and aggregate volume of white matter hyperintense (WMH) signals observed on proton density and T2-weighted brain MR images in a community sample of 177 adults ages 20 to 92. Using logistic regression, we tested whether participants with UA concentrations in the highest quartile of the sample—but still normal—would have increased WMH volumes.

Results: Compared with those with low to moderate levels, participants with high normal serum UA were more likely to fall in the highest quartile of WMH volume. The odds ratios (95% CIs) of increased WMH were 2.6 (1.2 to 5.4) for total, 2.5 (1.2 to 5.1) for periventricular, and 2.8 (1.4 to 5.9) for subcortical WMH volume. After controlling for age, sex, race, education, body mass, hypertension, and diabetes, the multivariate-adjusted odds of large total and subcortical WMH volumes remained elevated. Finally, high normal UA increased the odds of having excessive ischemic burden four- to fivefold in adults ages 60 and older.

Conclusions: These findings demonstrate that mildly elevated serum uric acid is associated with increased burden of cerebral ischemic pathology, particularly in older adults. We outline the potential pathogenesis of this association. A clinical trial of antihyperuricemic medication to treat or prevent chronic brain ischemia might be warranted.

GLOSSARY: ICC = intraclass correlation; OR = odds ratio; UA = uric acid; WMH = white matter hyperintense.

dschret{at}jhmi.edu

Supported by NIH/NIMH grants MH60504, MH52886, MH43775, and MH068522, the Therapeutic Cognitive Neuroscience Fund, and the Benjamin & Adith Miller Family Endowment on Aging, Alzheimer’s and Autism Research.

Disclosure: The authors report no conflicts of interest.

Received December 4, 2006. Accepted in final form April 27, 2007.

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