title: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  Treatment-, age-, and sex-adjusted 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 increase = 0.82; 95% CI, 0.73-0.93). In analyses stratified by alpha-tocopherol treatment (2000 IU/d), a decrease in the HR for the primary end point was seen only among subjects not treated with alpha-tocopherol (HR for a 1-SD increase = 0.75; 95% CI, 0.62-0.89; vs HR for those treated = 0.90; 95% CI, 0.75-1.08). Results were similar for the rate of change in the Unified Parkinson's Disease Rating Scale score. Cerebrospinal fluid urate concentration was also inversely related to both 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 Unified Parkinson's Disease Rating Scale score. As with serum urate concentration, these associations were present only among subjects not treated with alpha-tocopherol.
  
  
  CONCLUSIONS
  Higher serum and cerebrospinal fluid urate concentrations at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate concentration and PD and the rationale for considering central nervous system urate concentration elevation as a potential strategy to slow PD progression.
authors.affiliation: Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ascherio
authors.forename: Peter A
authors.initials: PA
authors.lastname: LeWitt
authors.forename: Kui
authors.initials: K
authors.lastname: Xu
authors.forename: Shirley
authors.initials: S
authors.lastname: Eberly
authors.forename: Arthur
authors.initials: A
authors.lastname: Watts
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Matson
authors.forename: Connie
authors.initials: C
authors.lastname: Marras
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
authors.forename: Alice
authors.initials: A
authors.lastname: Rudolph
authors.forename: Mikhail B
authors.initials: MB
authors.lastname: Bogdanov
authors.forename: Steven R
authors.initials: SR
authors.lastname: Schwid
authors.forename: Marsha
authors.initials: M
authors.lastname: Tennis
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Tanner
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: David
authors.initials: D
authors.lastname: Oakes
authors.forename: Stanley
authors.initials: S
authors.lastname: Fahn
authors.forename: Ira
authors.initials: I
authors.lastname: Shoulson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schwarzschild
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology*; D011237:Predictive Value of Tests; D014527:Uric Acid / Q000097:blood* / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D014527:Uric Acid