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Alberto Ascherio, MD, DrPH; Peter A. LeWitt, MD; Kui Xu, MD, PhD; Shirley Eberly, MS; Arthur Watts, BS; Wayne R. Matson, PhD; Connie Marras, MD; Karl Kieburtz, MD; Alice Rudolph, PhD; Mikhail B. Bogdanov, PhD; Steven R. Schwid, MD; Marsha Tennis, RN; Caroline M. Tanner, MD, PhD; M. Flint Beal, MD; Anthony E. Lang, MD; David Oakes, PhD; Stanley Fahn, MD; Ira Shoulson, MD; Michael A. Schwarzschild, MD, PhD; for the Parkinson Study Group DATATOP Investigators

Arch Neurol. 2009;66(12):(doi:10.1001/archneurol.2009.247).

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 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 -tocopherol treatment (2000 IU/d), a decrease in the HR for the primary end point was seen only among subjects not treated with -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 -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.

Author Affiliations: Departments of Nutrition and Epidemiology, Harvard School of Public Health (Dr Ascherio), Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School (Dr Ascherio), and Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital (Drs Xu and Schwarzschild and Ms Tennis), Boston, and Bedford Veterans Administration Medical Center, Bedford (Drs Matson and Bogdanov); Department of Neurology, Henry Ford Hospital and Wayne State University School of Medicine, Detroit, Michigan (Dr LeWitt); Departments of Biostatistics (Ms Eberly, Mr Watts, and Dr Oakes) and Neurology (Drs Kieburtz, Rudolph, Schwid, and Shoulson), University of Rochester, Rochester, and Department of Neurology and Neuroscience, Cornell University (Dr Beal) and Department of Neurology, Columbia University (Dr Fahn), New York, New York; The Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada (Drs Marras and Lang); and Department of Clinical Research, Parkinson's Institute, Sunnyvale, California (Dr Tanner).
Group Information: A list of the Parkinson Study Group DATATOP Investigators was published in N Engl J Med. 1993;328(3):176-183.
Deceased.

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