Serum Urate as a Predictor of Clinical and Radiographic Progression in Parkinson Disease

• Published in: Archives of neurology (Chicago) Vol. 65; no. 6; pp. 716 - 723
• Main Authors: Schwarzschild, Michael A, Schwid, Steven R, Marek, Kenneth, Watts, Arthur, Lang, Anthony E, Oakes, David, Shoulson, Ira, Ascherio, Alberto
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 01.06.2008
• Subjects: Antioxidants; Biomarkers - blood; Cohort Studies; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Medical prognosis; Medical research; Middle Aged; Neurology; Parkinson Disease - blood; Parkinson Disease - diagnosis; Parkinson Disease - diagnostic imaging; Parkinson's disease; Predictive Value of Tests; Prospective Studies; Radiography; Uric Acid - blood
• ISSN: 0003-9942; 2168-6149; 1538-3687; 2168-6157
• DOI: 10.1001/archneur.2008.65.6.nct70003

OBJECTIVE To determine whether concentration of serum urate, a purine metabolite and potent antioxidant that has been linked to a reduced risk of Parkinson disease (PD), predicts prognosis in PD. DESIGN Prospective study. SETTING The Parkinson Research Examination of CEP-1347 Trial (PRECEPT) study, which investigated the effects of a potential neuroprotectant on rates of PD progression, was conducted between April 2002 and August 2005 (average follow-up time 21.4 months). PARTICIPANTS Eight hundred four subjects with early PD enrolled in the PRECEPT study. MAIN OUTCOME MEASURES The primary study end point was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching end point according to quintiles of baseline serum urate concentration, adjusting for sex, age, and other potential covariates. Change in striatal uptake of iodine I 123–labeled 2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([123I]β-CIT), a marker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects. RESULTS The adjusted HR of reaching end point declined with increasing baseline concentrations of urate; subjects in the top quintile reached the end point at only half the rate of subjects in the bottom quintile (HR, 0.51; 95% confidence interval [CI], 0.37-0.72; Pfor trend < .001). This association was markedly stronger in men (HR, 0.39; 95% CI, 0.26-0.60; Pfor trend < .001) than in women (HR, 0.77; 95% CI, 0.39-1.50; Pfor trend = .33). The percentage of loss in striatal [123I]β-CIT uptake also improved with increasing serum urate concentrations (overall Pfor trend = .002; men, P = .001; women, P = .43). CONCLUSIONS These findings identify serum urate as the first molecular factor directly linked to the progression of typical PD and suggest that targeting urate or its determinants could be an effective disease-modifying therapy in PD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00040404.Published online April 14, 2008 10.1001/archneur.2008.65.6.nct70003 Arch Neurol. 2008;65(6):716-723-->