Increased Ischemic Burden Linked to Elevated Uric Acid Levels

Caroline Cassels

October 04, 2007

October 4, 2007 — Mildly elevated levels of uric acid (UA) have been linked to a high volume of white-matter hyperintensities (WMH) in aging adults, a finding that confirms the role of UA in increasing the risk for cerebrovascular disease and that may also explain the link between elevated UA and mild cognitive impairment (MCI) in aging adults.

A study by investigators at Johns Hopkins University School of Medicine, in Baltimore, Maryland, found that individuals with high-normal UA levels had 2.6 times the volume of WMH compared with those with average or low UA.

They also found individuals aged 60 years and older with high-normal UA levels had 4- to 5-fold increased odds of having excessive ischemic burden.

"Given that high-normal serum uric acid appears to be a biomarker of mild cognitive impairment in elderly adults, the current results suggest that determining whether UA-lowering medications can reduce ischemic brain disease or improve cognitive functioning in elderly adults with mildly elevated uric acid merits consideration," the authors write.

Led by David Schretlen, PhD, the study is published in the October 2 issue of Neurology.

Powerful Antioxidant

Once thought to be a metabolically inert end-product of purine, the authors note that UA is now being recognized as a potent antioxidant whose concentration in plasma is nearly 10 times higher than that of other antioxidants, including vitamins C and E.

Some research suggests UA may be neuroprotective and reduce the risk for neurological conditions, including Alzheimer's disease. A recent study by researchers at Harvard School of Public Health found high levels of UA were associated with a decreased risk for Parkinson's disease (PD), a finding that may ultimately have implications for slowing PD progression (Weisskopf MG et al. Am J Epidemiol. 2007;166:561-567).

On the other hand, even mildly elevated UA levels have been linked to an increased risk for hypertension, type 2 diabetes, stroke, and fatal cardiovascular events, as well as mild cognitive impairment.

Recent research by Dr. Schretlen and colleagues looked at the relationship between serum UA and cognitive functioning in adults over the age of 65 years and found those with high-normal UA levels were 2.7 to 5.9 times more likely to score in the lowest quartile of the study sample on measures of processing speed, verbal memory, and working memory.

Broad Public Health Implications

In the current study, investigators sought to examine the relationship between serum UA and WMH volume. The community-based, cross-sectional, observational study included 177 men and women between the ages of 20 and 92 years.

All study subjects underwent a physical and neurologic examination, psychiatric review, laboratory blood studies, and psychoneurological testing. T2- weighted brain magnetic resonance imaging (MRI) and proton density scans were used to measure aggregate WMH volume.

Serum UA concentrations ranged from 1.5 to 7.2 mg/dL for women and 1.6 to 8.2 mg/dL for men. Concentrations of 5.75 mg/dL or greater for men and 4.8 mg/dL or greater for women were classified as high-normal.

Compared with individuals with low to moderate UA levels, participants with high-normal serum UA were more likely to fall in the highest quartile of WMH volume.

This was particularly pronounced in those older than 65 years, where high-normal serum UA was significantly associated with an excessive cerebral ischemic burden.

According to Dr. Schretlen, clinical trials with UA-lowering agents such as allopurinal, which have proven long-term safety and efficacy, may be warranted if further research confirms the link between UA and WMH.

The authors also pointed out that because these data were based on a representative community sample, the study's finding that even normal elevations of serum UA are associated with an increased burden of WMH could have broad public health implications.

The study was supported by the National Institutes of Health/National Institute of Mental Health, the Therapeutic Cognitive Neuroscience Fund, and the Benjamin & Adith Miller Family Endowment on Aging, Alzheimer's, and Autism Research.

Neurology. 2007;69:1418-1423. Abstract


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