Urate as a Predictor of the Rate of Clinical Decline in Parkinson Disease
Identifieur interne : 002057 ( Main/Exploration ); précédent : 002056; suivant : 002058Urate as a Predictor of the Rate of Clinical Decline in Parkinson Disease
Auteurs : Alberto Ascherio [États-Unis] ; Peter A. Lewitt [États-Unis] ; KUI XU [États-Unis] ; Shirley Eberly [États-Unis] ; Arthur Watts [États-Unis] ; Wayne R. Matson [États-Unis] ; Connie Marras [Canada] ; Karl Kieburtz [États-Unis] ; Alice Rudolph [États-Unis] ; Mikhail B. Bogdanov [États-Unis] ; Steven R. Schwid [États-Unis] ; Marsha Tennis [États-Unis] ; Caroline M. Tanner [États-Unis] ; M. Flint Beal [États-Unis] ; Anthony E. Lang [Canada] ; David Oakes [États-Unis] ; Stanley Fahn [États-Unis] ; Ira Shoulson [États-Unis] ; Michael A. Schwarzschild [États-Unis]Source :
- Archives of neurology : (Chicago) [ 0003-9942 ] ; 2009.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
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 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 α-tocopherol treatment (2000 IU/d), a decrease in the HR for the primary end point was seen only among subjects not treated with α-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 α-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.
Affiliations:
- Canada, États-Unis
- Californie, Massachusetts, Michigan, Ontario, État de New York
- Boston, Ithaca (New York), New York, Toronto
- Université Columbia, Université Cornell, Université de Toronto
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Lewitt</name><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Neurology, Henry Ford Hospital and Wayne State University School of Medicine</s1><s2>Detroit, Michigan</s2><s3>USA</s3><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Kui Xu" sort="Kui Xu" uniqKey="Kui Xu" last="Kui Xu">KUI XU</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Eberly, Shirley" sort="Eberly, Shirley" uniqKey="Eberly S" first="Shirley" last="Eberly">Shirley Eberly</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Biostatistics, University of Rochester</s1><s2>Rochester</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester</wicri:noRegion></affiliation></author><author><name sortKey="Watts, Arthur" sort="Watts, Arthur" uniqKey="Watts A" first="Arthur" last="Watts">Arthur Watts</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Biostatistics, University of Rochester</s1><s2>Rochester</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester</wicri:noRegion></affiliation></author><author><name sortKey="Matson, Wayne R" sort="Matson, Wayne R" uniqKey="Matson W" first="Wayne R." last="Matson">Wayne R. Matson</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Bedford Veterans Administration Medical Center</s1><s2>Bedford</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bedford Veterans Administration Medical Center</wicri:noRegion></affiliation></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name><affiliation wicri:level="4"><inist:fA14 i1="10"><s1>Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurology, University of Rochester</s1><s2>Rochester</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester</wicri:noRegion></affiliation></author><author><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurology, University of Rochester</s1><s2>Rochester</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester</wicri:noRegion></affiliation></author><author><name sortKey="Bogdanov, Mikhail B" sort="Bogdanov, Mikhail B" uniqKey="Bogdanov M" first="Mikhail B." last="Bogdanov">Mikhail B. Bogdanov</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Bedford Veterans Administration Medical Center</s1><s2>Bedford</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bedford Veterans Administration Medical Center</wicri:noRegion></affiliation></author><author><name sortKey="Schwid, Steven R" sort="Schwid, Steven R" uniqKey="Schwid S" first="Steven R." last="Schwid">Steven R. Schwid</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurology, University of Rochester</s1><s2>Rochester</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester</wicri:noRegion></affiliation></author><author><name sortKey="Tennis, Marsha" sort="Tennis, Marsha" uniqKey="Tennis M" first="Marsha" last="Tennis">Marsha Tennis</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="11"><s1>Department of Clinical Research, Parkinson's Institute</s1><s2>Sunnyvale, California</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline M." last="Tanner">Caroline M. Tanner</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Beal, M Flint" sort="Beal, M Flint" uniqKey="Beal M" first="M. Flint" last="Beal">M. Flint Beal</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Department of Neurology and Neuroscience, Cornell University</s1><s3>USA</s3><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Ithaca (New York)</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Cornell</orgName></affiliation></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><affiliation wicri:level="4"><inist:fA14 i1="10"><s1>Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Oakes, David" sort="Oakes, David" uniqKey="Oakes D" first="David" last="Oakes">David Oakes</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Biostatistics, University of Rochester</s1><s2>Rochester</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester</wicri:noRegion></affiliation></author><author><name sortKey="Fahn, Stanley" sort="Fahn, Stanley" uniqKey="Fahn S" first="Stanley" last="Fahn">Stanley Fahn</name><affiliation wicri:level="4"><inist:fA14 i1="09"><s1>Department of Neurology, Columbia University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region><settlement type="city">New York</settlement></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Shoulson, Ira" sort="Shoulson, Ira" uniqKey="Shoulson I" first="Ira" last="Shoulson">Ira Shoulson</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurology, University of Rochester</s1><s2>Rochester</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester</wicri:noRegion></affiliation></author><author><name sortKey="Schwarzschild, Michael A" sort="Schwarzschild, Michael A" uniqKey="Schwarzschild M" first="Michael A." last="Schwarzschild">Michael A. Schwarzschild</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Archives of neurology : (Chicago)</title><title level="j" type="abbreviated">Arch. neurol. : (Chic.)</title><idno type="ISSN">0003-9942</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Archives of neurology : (Chicago)</title><title level="j" type="abbreviated">Arch. neurol. : (Chic.)</title><idno type="ISSN">0003-9942</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Nervous system diseases</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 α-tocopherol treatment (2000 IU/d), a decrease in the HR for the primary end point was seen only among subjects not treated with α-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 α-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.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Californie</li><li>Massachusetts</li><li>Michigan</li><li>Ontario</li><li>État de New York</li></region><settlement><li>Boston</li><li>Ithaca (New York)</li><li>New York</li><li>Toronto</li></settlement><orgName><li>Université Columbia</li><li>Université Cornell</li><li>Université de Toronto</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="Ascherio, Alberto" sort="Ascherio, Alberto" uniqKey="Ascherio A" first="Alberto" last="Ascherio">Alberto Ascherio</name></noRegion><name sortKey="Ascherio, Alberto" sort="Ascherio, Alberto" uniqKey="Ascherio A" first="Alberto" last="Ascherio">Alberto Ascherio</name><name sortKey="Beal, M Flint" sort="Beal, M Flint" uniqKey="Beal M" first="M. Flint" last="Beal">M. Flint Beal</name><name sortKey="Bogdanov, Mikhail B" sort="Bogdanov, Mikhail B" uniqKey="Bogdanov M" first="Mikhail B." last="Bogdanov">Mikhail B. Bogdanov</name><name sortKey="Eberly, Shirley" sort="Eberly, Shirley" uniqKey="Eberly S" first="Shirley" last="Eberly">Shirley Eberly</name><name sortKey="Fahn, Stanley" sort="Fahn, Stanley" uniqKey="Fahn S" first="Stanley" last="Fahn">Stanley Fahn</name><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name><name sortKey="Kui Xu" sort="Kui Xu" uniqKey="Kui Xu" last="Kui Xu">KUI XU</name><name sortKey="Lewitt, Peter A" sort="Lewitt, Peter A" uniqKey="Lewitt P" first="Peter A." last="Lewitt">Peter A. Lewitt</name><name sortKey="Matson, Wayne R" sort="Matson, Wayne R" uniqKey="Matson W" first="Wayne R." last="Matson">Wayne R. Matson</name><name sortKey="Oakes, David" sort="Oakes, David" uniqKey="Oakes D" first="David" last="Oakes">David Oakes</name><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name><name sortKey="Schwarzschild, Michael A" sort="Schwarzschild, Michael A" uniqKey="Schwarzschild M" first="Michael A." last="Schwarzschild">Michael A. Schwarzschild</name><name sortKey="Schwid, Steven R" sort="Schwid, Steven R" uniqKey="Schwid S" first="Steven R." last="Schwid">Steven R. Schwid</name><name sortKey="Shoulson, Ira" sort="Shoulson, Ira" uniqKey="Shoulson I" first="Ira" last="Shoulson">Ira Shoulson</name><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline M." last="Tanner">Caroline M. Tanner</name><name sortKey="Tennis, Marsha" sort="Tennis, Marsha" uniqKey="Tennis M" first="Marsha" last="Tennis">Marsha Tennis</name><name sortKey="Tennis, Marsha" sort="Tennis, Marsha" uniqKey="Tennis M" first="Marsha" last="Tennis">Marsha Tennis</name><name sortKey="Watts, Arthur" sort="Watts, Arthur" uniqKey="Watts A" first="Arthur" last="Watts">Arthur Watts</name></country><country name="Canada"><region name="Ontario"><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name></region><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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