Urate as a Predictor of the Rate of Clinical Decline in Parkinson Disease

Abstract

Background:The risk of Parkinson disease (PD) and its rate of progression may decline with increasing concentration of blood urate, a major antioxidant.Objective: To determine whether serum and cerebrospinal fluid concentrations of urate predict clinical progression in patients with PD.Design, Setting, and Participants: Eight hundred subjects with early PD enrolled in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. The pretreatment urate concentration was measured in serum for 774 subjects and in cerebrospinal fluid for 713 subjects.Main Outcome Measures: Treatment-, age-, and sexadjusted hazard ratios (HRs) for clinical disability requiring levodopa therapy, the prespecified primary end point of the original DATATOP trial. Results:The HR of progressing to the primary end point decreased with increasing serum urate concentrations (HR for highest vs lowest quintile = 0.64; 95% confidence interval [CI], 0.44-0.94; HR for a 1-SD Author Affiliations are listed at the end of this article.

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

“…In the PRECEPT clinical trial, the risk of PD disability progressing to the need for dopaminergic therapy among those in the highest quintile of serum urate concentration at baseline was half that of the lowest quintile [22]. Similarly, in the DATATOP clinical trial, risk of PD progression was reduced by 18% for each 1.5 mg/dl increase in serum urate concentration, with a similar inverse correlation between CSF urate and progression [23]. A causal link between urate levels and PD outcomes is strengthened by the finding that genetic determinants of urate levels also predict PD disease progression [24].…”

“…Progression Inverse association [22][23][24] Inverse association [25][26][27][28] No association [29,30] Inverse association in HD, MSA, MCI [31][32][33] Laboratory…”

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…Higher serum uric acid concentration has been linked also to slower clinical progression of PD [665,666].…”

Clinically Useful Biomarkers for Parkinson’s Disease

“…Other small molecules of interest are glutathione and purine metabolites, including uric acid, because of their role as antioxidants [45,46].…”