Serum and CSF Urate Levels May Predict Parkinson Disease Progression
November 9, 2009
Urate is a superoxide, peroxynitrite and hydroxyl radical scavenger, and iron chelator and ascorbate stabilizer. Previous research has shown that people with higher urate levels are at a lower risk of Parkinson disease (PD), by virtue of its antioxidant effect. These include persons with gout and those who consume diets which increase serum urate levels, such as sweetbreads, certain types of fish, and organ meats, including liver, kidney and brain. Now, a study, published in the latest issue of Archives of Neurology, has reported that serum and cerebrospinal fluid (CSF) urate levels may predict the rate of clinical decline in PD.
Alberto Ascherio, Professor at the Departments of Nutrition and Epidemiology, Harvard School of Public Health, and colleagues, conducted the 2-year, multicentered, double-blind, randomized trial on 800 subjects affected with early PD (Hoehn and Yahr stages 1 and 2) for less than 5 years. The study utilized the clinical database of the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism [DATATOP] trial, which intended on determining if long-term treatment of early PD with selegiline hydrochloride and/or alpha-tocopherol could delay the onset of disability, which would require treatment with levodopa. Baseline (pretreatment) urate concentrations in the serum of 774 subjects and CSF urate levels in 713 patients were measured, and subjects were followed up for every 3 months. The primary end point of the study was the appearance of disability, sufficient to start dopaminergic treatment, and secondary variables included the responses to the Unified Parkinson’s Disease Rating Scale (UPDRS) score (sum of the cognitive, motor, and activity of daily living subscale scores).
For the subjects with available serum urate concentration, 369 (47.7%) reached the primary end points. It was observed that the hazard ratio of progressing to the primary end point was inversely proportional to the serum urate concentrations (HR for highest vs. lowest quintile=0.64, 95% CI=0.44-0.94; HR for a 1-SD increase=0.82, 95% CI=0.73-0.93). For the subjects with available CSF urate levels, a total of 342 (48%) reached the primary end point. The CSF urate concentration was inversely related to the primary end point (HR for highest vs. lowest quintile=0.65, 95% CI=0.44-0.96; HR for a 1-SD increase=0.89; 95% CI=0.79-1.02) and the rate of change in the UPDRS.
In another study by Andreadou et al (Clinical Neurology and Neurosurgery, 2009), conducted on 43 PD patients and 47 age- and sex-matched healthy volunteers, it was reported that serum uric acid (UA) was lower in the PD patients compared to the control group (P=0.009). An inverse correlation between UA, and disease duration and levodopa dosage was also observed; which was significant in men but not in women. However, age, body mass index (BMI) and UPDRS III score did not significantly influence the UA concentrations. As expected, gender correlated with the UA levels.
An earlier cohort study by De Vera et al (Arthritis and Rheumatism, 2008) reported that gout has a protective effect on PD. The conclusion was based on a population-based study with an objective to determine the incidence rates of PD in 11,258 gout patients and 56,199 appropriately matched control subjects. A total of 1,182 new cases of PD were reported during the 8-year median follow up. The relative risk of PD in patients with gout as compared to those without the disease was 0.70 (95% CI=0.59-0.83).
According to the National Institute of Neurological Disorders and Stroke (NINDS), PD is estimated to affect more than a million people across the United States. The disease is characterized by disabling symptoms including tremors, bradykinesia, rigidity and postural instability. Although pharmacological and surgical treatment offers symptomatic relief to patients, there is no definite cure for the disease. Newer therapies like stem cell-based therapy hold promise as a therapeutic strategy. In addition, based on the current study, manipulation of urate levels by a readily available, urate precursor inosine could have beneficial effects in PD. However, determining if the neuroprotective effects of increased urate levels outweigh the cardiovascular risk it poses, needs to be ascertained by further studies.
References
1. Ascherio A, Lewitt PA, Xu K, et al. Urate as a Predictor of the Rate of Clinical Decline in Parkinson Disease. Arch Neurol. 2009 Oct 12.
2. Andreadou E, Nikolaou C, Gournaras F, et al. Serum uric acid levels in patients with Parkinson’s disease: their relationship to treatment and disease duration. Clin Neurol Neurosurg. 2009 Nov;111(9):724-8.
3. De Vera M, Rahman MM, Rankin J, Kopec J, Gao X, Choi H. Gout and the risk of Parkinson’s disease: a cohort study. Arthritis Rheum. 2008 Nov 15;59(11):1549-54.
4. Parkinson’s disease research web overview. National Institute of Neurological Disorders and Stroke. Last accessed October 21, 2009
5. Weisskopf MG, O’Reilly E, Chen H, Schwarzschild MA, Ascherio A. Plasma urate and risk of Parkinson’s disease. Am J Epidemiol. 2007 Sep 1;166(5):561-7. Epub 2007 Jun 20.
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