Urate as a predictor of the rate of clinical decline in Parkinson disease.
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.
Ascherio
Alberto
A
Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
LeWitt
Peter A
PA
Xu
Kui
K
Eberly
Shirley
S
Watts
Arthur
A
Matson
Wayne R
WR
Marras
Connie
C
Kieburtz
Karl
K
Rudolph
Alice
A
Bogdanov
Mikhail B
MB
Schwid
Steven R
SR
Tennis
Marsha
M
Tanner
Caroline M
CM
Beal
M Flint
MF
Lang
Anthony E
AE
Oakes
David
D
Fahn
Stanley
S
Shoulson
Ira
I
Schwarzschild
Michael A
MA
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*
D015415:Biomarkers; D014527:Uric Acid