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The newspaper of The Johns Hopkins University December 10, 2007 | Vol. 37 No. 14
Barely Detectable Mini Strokes Linked to Uric Acid Levels

Findings could explain mental decline in some older adults

By Eric Vohr
Johns Hopkins Medicine

Researchers at Johns Hopkins have found that high-normal uric acid 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 uric acid 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 Neurology, lead author David Schretlen, of the Department of Psychiatry in the School of Medicine, linked uric acid levels to high volumes of so-called white matter hyperintensities, or 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 is a hallmark of classic large strokes.

"Over a lifetime, it is common to have a small number of these mini strokes and not even notice," Schretlen said, "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 uric acid is best known in gout, where buildup of the fatty acid creates pain and disability in the feet and toes. However, uric acid appears to play contradictory roles in the brain, Schretlen says. For example, uric acid is a powerful antioxidant that might even protect against Parkinson's and Alzheimer's diseases, possibly because antioxidants destroy oxygen free radicals that damage tissue. On the other hand, elevated uric acid 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, uric acid is beneficial, but processes leading to its production can be harmful under some circumstances, Schretlen says.

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 uric acid. However, those with high-normal levels showed 2.6 times the volume of WMH than those with average or low uric acid. Among subjects 60 years of age or older, those with high-normal levels of uric acid had four to five times the volume of WMH than others.

Gender differences exist in normal uric acid ranges. The blood uric acid concentrations of men are typically about 1 milligram per deciliter higher than those of women. In this study, uric acid 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 uric acid 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 uric acid levels are linked to both mild cognitive decline and mini strokes," Schretlen said, "we need to learn how these are related. We have to find out which of these factors steers the boat."

Schretlen says that 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 School of Medicine, are Anjeli B. Inscore, Tracy D. Vannorsdall and Godfrey D. Pearlson, of Psychiatry and Behavioral Sciences; Barry Gordon and H.A. Jinnah, of Neurology; and Michael Kraut, of Radiology and Radiological Science.


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