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
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
"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
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,
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
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.