The role of uric acid in bodily homeostasis is puzzling to investigators. On one hand, it is a potent antioxidant. On the other, elevated levels have been consistently been associated with an increase in vascular events, including stroke. Thus, it is unclear whether interventions designed to decrease uric acid will be beneficial in preventing vascular events. Here, Schretlen et al (Neurology 2007;69:1418) explore the association of serum uric acid levels with brain changes in adults using magnetic resonance imaging (MRI).
Community dwelling adults age 65 and older without high serum uric acid levels (defined at < 9.2 mg/dL) underwent brain MRI, assessed for cerebral white matter hyper-intense (WMH) lesions. The association between cross-sectional serum uric acid and WMH lesions was examined.
There were 177 subjects enrolled (52% Female) with a mean age of around 60 years. The average body mass index (BMI) was approximately 27 ± 5 kg/m2. Approximately a third of subjects were hypertensive and approximately 13% had diabetes. Of the subject characteristics, serum uric acid level was significantly associated with increasing age, increasing BMI, male gender, and presence of hypertension, but was not significantly associated with presence of diabetes, smoking, or history of alcohol abuse.
In univariate models, subjects with high normal serum uric acid levels (5.75 – 9.2 mg/dL for men, 4.8 – 9.2 mg/dL for women) had a 2.6 fold higher odds of total WMH lesions compared to those with lower uric acid levels (95% CI 1.25 – 5.40), with an equal odds of subcortical and periventricular involvement. In multivariate models adjusted for age, gender, race, education, hypertension, and diabetes, the odds of total WMH lesions in subjects with high normal uric acid levels was even higher vs, those with lower uric acid levels (OR 2.78 (95% CI 1.10 – 7.01)). Stratified analyses revealed that the association was similar in men and women, strongest in older subjects (age 60+), and was maintained even when subjects with competing comorbidities (i.e. severe health problems, dementia, and cognitive impairment) were excluded.
High normal serum uric acid levels are associated with cerebral white matter ischemic changes of the brain.
Even though patients with uric acid levels in the range in which a diagnosis of gout would be expected were not included in this study, these findings are likely to be accentuated in gout patients. Patients with gout have a number of associated comorbidities that make them more susceptible to microvascular brain ischemia (i.e. atherosclerosis, hypertension, etc…), but these data suggest that the net effect of serum uric acid itself may lead to pathogenic changes in the brain, even though uric acid is known to have antioxidant properties. Efforts to reduce serum uric acid levels, even in those with high normal levels, may help to preserve cognitive function as patients age.