ScienceDaily (Oct. 5, 2007) — Researchers at Johns Hopkins have found that high-normal uric acid (UA) levels may cause barely detectable mini strokes that potentially contribute to mental decline in aging adults.

Diet, exercise and drugs like allopurinol (all of which lower UA levels) could eventually be of value in reducing this risk, especially for those with additional risk factors such as diabetes, obesity and hypertension, the researchers say. But they caution that it would be premature to try this now.

In a study published in the Oct. 2 issue of Neurology, lead author David Schretlen, Ph.D., of the Department of Psychiatry at The Johns Hopkins University School of Medicine, linked UA levels to high volumes of so-called white matter hyperintensities (WMH), which are small dead areas of the brain that occur when brain cells are deprived of oxygen. Lack of oxygen due to clots or burst blood vessels in the brain are hallmarks of classic large strokes.

"Over a lifetime, it is common to have a small number of these mini strokes and not even notice," says Schretlen, "but as the overall volume of WMH increases, the damage can seriously disrupt how quickly we think and how effectively we learn and remember information."

The role of UA is best known in gout, where buildup of the fatty acid creates pain and disability in the feet and toes. However, UA appears to play contradictory roles in the brain, says Schretlen. For example, UA is a powerful antioxidant that might even protect against Parkinson disease and Alzheimer disease, possibly because antioxidants destroy oxygen free radicals that damage tissue.

On the other hand, elevated UA accompanies diabetes, obesity and heart disease, and it is a well-known risk factor for stroke. One possible explanation of its seemingly contradictory nature is that, like a double-edged sword, UA is beneficial, but processes leading to its production can be harmful under some circumstances, says Schretlen.

In the study, Schretlen and his team obtained and analyzed brain MRI scans of 85 men and 92 women between 20 and 92 years of age. All participants had normal levels of UA. However, those with high-normal levels showed 2.6 times the volume of WMH than those with average or low UA. Among subjects 60 years of age or older, those with high-normal levels of UA had four to five times the volume of WMH than others.

Gender differences exist in normal UA ranges. The blood UA concentrations of men are typically about 1 milligram per deciliter (mg/dL) higher than those of women. In this study UA levels ranged from 1.6 to 8.2 mg/dL for men and from 1.5 to 7.2 mg/dL for women. Within these ranges, concentrations greater than or equal to 5.75 mg/dL for men and 4.8 mg/dL for women were classified as high normal.

In a previous study, Schretlen and colleagues examined the relationship between serum UA and cognitive functioning in adults age 60 and older. In that study, elderly adults with high-normal levels of UA were 2.7 to 5.9 times more likely to score in the lowest 25 percent of the group on measures of thinking speed and memory.

"Having found that UA levels are linked to both mild cognitive decline and mini strokes," says Schretlen, "we need to learn how these are related. We have to find out which of these factors steers the boat."

Schretlen says clinical trials with drugs like allopurinol, which have been used safely for decades to treat gout, may be warranted if further research confirms his hypothesis.

Additional authors of this study, all from The Johns Hopkins University School of Medicine, are Anjeli B. Inscore, Psy.D., Tracy D. Vannorsdall, Ph.D., and Godfrey D. Pearlson, M.D., of the Department of Psychiatry and Behavioral Sciences; Barry Gordon, M.D., Ph.D., and H.A. Jinnah, M.D., Ph.D., of the Department of Neurology, and Michael Kraut, M.D., Ph.D., of the Department of Radiology and Radiological Sciences.

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Adapted from materials provided by Johns Hopkins Medical Institutions.

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