Serum urate as a predictor of clinical and radiographic progression in Parkinson disease.
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.


METHODS
Prospective study.


METHODS
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).


METHODS
Eight hundred four subjects with early PD enrolled in the PRECEPT study.


METHODS
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 ([(123)I]beta-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; P for trend < .001). This association was markedly stronger in men (HR, 0.39; 95% CI, 0.26-0.60; P for trend < .001) than in women (HR, 0.77; 95% CI, 0.39-1.50; P for trend = .33). The percentage of loss in striatal [(123)I]beta-CIT uptake also improved with increasing serum urate concentrations (overall P for 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.
Schwarzschild
Michael A
MA
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, USA.
Schwid
Steven R
SR
Marek
Kenneth
K
Watts
Arthur
A
Lang
Anthony E
AE
Oakes
David
D
Shoulson
Ira
I
Ascherio
Alberto
A
Hyson
Christopher
C
Gorbold
Emily
E
Rudolph
Alice
A
Kieburtz
Karl
K
Fahn
Stanley
S
Gauger
Lisa
L
Goetz
Christopher
C
Seibyl
John
J
Forrest
Misser
M
Ondrasik
John
J
D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011859:Radiography; D014527:Uric Acid / Q000097:blood*
D015415:Biomarkers; D014527:Uric Acid