1!Serum urate as a predictor of clinical and radiographic progression in Parkinson’s disease
Identifieur interne : 000179 ( Ncbi/Checkpoint ); précédent : 000178; suivant : 0001801!Serum urate as a predictor of clinical and radiographic progression in Parkinson’s disease
Auteurs : Michael Schwarzschild ; Steven Schwid ; Kenneth Marek ; Arthur Watts ; Anthony Lang ; David Oakes ; Ira Shoulson ; Alberto AscherioSource :
- Archives of neurology [ 0003-9942 ] ; 2008.
English descriptors
- KwdEn :
- Biomarkers (blood), Cohort Studies, Disease Progression, Double-Blind Method, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Parkinson Disease (blood), Parkinson Disease (diagnosis), Parkinson Disease (radiography), Predictive Value of Tests, Prospective Studies, Uric Acid (blood).
- MESH :
- chemical , blood : Biomarkers, Uric Acid.
- blood : Parkinson Disease.
- diagnosis : Parkinson Disease.
- radiography : Parkinson Disease.
- Cohort Studies, Disease Progression, Double-Blind Method, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Predictive Value of Tests, Prospective Studies.
Abstract
Prospective epidemiological studies consistently indicate that Parkinson’s disease (PD) risk declines with increasing serum urate.
To determine whether serum urate, a purine metabolite and potent antioxidant, predicts prognosis in PD.
Prospective study among 804 subjects with early PD enrolled in the PRECEPT study, a clinical trial of the neuroprotectant potential of CEP-1347, conducted between April 2002 and August 2005 (average follow-up time 21.4 months).
The primary study endpoint was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching endpoint according to quintiles of baseline serum urate, adjusting for gender, age and other potential covariates. Change in striatal uptake of [123I]β-CIT, a marker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects.
The adjusted HR of reaching endpoint declined with increasing baseline concentrations of urate; subjects in the top quintile reached the endpoint at only half the rate of subjects in the bottom quintile (HR=0.51; 95% CI: 0.37 to 0.72; p=0.0002). This association was markedly stronger in men (HR=0.39; 95% CI: 0.26 to 0.60; p<0.0001) than in women (HR=0.77; 95% CI: 0.39 to 1.50; p=0.4). The percent loss in striatal [123I]β-CIT uptake also improved with increasing serum urate concentrations (overall p for trend=0.002; men, p=0.0008; women, p= 0.4).
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.
Url:
DOI: 10.1001/archneur.2008.65.6.nct70003
PubMed: 18413464
PubMed Central: 2574855
Affiliations:
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PMC:2574855Le document en format XML
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<author><name sortKey="Schwarzschild, Michael A" sort="Schwarzschild, Michael A" uniqKey="Schwarzschild M" first="Michael" last="Schwarzschild">Michael Schwarzschild</name>
</author>
<author><name sortKey="Schwid, Steven R" sort="Schwid, Steven R" uniqKey="Schwid S" first="Steven" last="Schwid">Steven Schwid</name>
</author>
<author><name sortKey="Marek, Kenneth" sort="Marek, Kenneth" uniqKey="Marek K" first="Kenneth" last="Marek">Kenneth Marek</name>
</author>
<author><name sortKey="Watts, Arthur" sort="Watts, Arthur" uniqKey="Watts A" first="Arthur" last="Watts">Arthur Watts</name>
</author>
<author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony" last="Lang">Anthony Lang</name>
</author>
<author><name sortKey="Oakes, David" sort="Oakes, David" uniqKey="Oakes D" first="David" last="Oakes">David Oakes</name>
</author>
<author><name sortKey="Shoulson, Ira" sort="Shoulson, Ira" uniqKey="Shoulson I" first="Ira" last="Shoulson">Ira Shoulson</name>
</author>
<author><name sortKey="Ascherio, Alberto" sort="Ascherio, Alberto" uniqKey="Ascherio A" first="Alberto" last="Ascherio">Alberto Ascherio</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">1!Serum urate as a predictor of clinical and radiographic progression in Parkinson’s disease</title>
<author><name sortKey="Schwarzschild, Michael A" sort="Schwarzschild, Michael A" uniqKey="Schwarzschild M" first="Michael" last="Schwarzschild">Michael Schwarzschild</name>
</author>
<author><name sortKey="Schwid, Steven R" sort="Schwid, Steven R" uniqKey="Schwid S" first="Steven" last="Schwid">Steven Schwid</name>
</author>
<author><name sortKey="Marek, Kenneth" sort="Marek, Kenneth" uniqKey="Marek K" first="Kenneth" last="Marek">Kenneth Marek</name>
</author>
<author><name sortKey="Watts, Arthur" sort="Watts, Arthur" uniqKey="Watts A" first="Arthur" last="Watts">Arthur Watts</name>
</author>
<author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony" last="Lang">Anthony Lang</name>
</author>
<author><name sortKey="Oakes, David" sort="Oakes, David" uniqKey="Oakes D" first="David" last="Oakes">David Oakes</name>
</author>
<author><name sortKey="Shoulson, Ira" sort="Shoulson, Ira" uniqKey="Shoulson I" first="Ira" last="Shoulson">Ira Shoulson</name>
</author>
<author><name sortKey="Ascherio, Alberto" sort="Ascherio, Alberto" uniqKey="Ascherio A" first="Alberto" last="Ascherio">Alberto Ascherio</name>
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<series><title level="j">Archives of neurology</title>
<idno type="ISSN">0003-9942</idno>
<idno type="e-ISSN">1538-3687</idno>
<imprint><date when="2008">2008</date>
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<term>Cohort Studies</term>
<term>Disease Progression</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Follow-Up Studies</term>
<term>Humans</term>
<term>Longitudinal Studies</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Parkinson Disease (blood)</term>
<term>Parkinson Disease (diagnosis)</term>
<term>Parkinson Disease (radiography)</term>
<term>Predictive Value of Tests</term>
<term>Prospective Studies</term>
<term>Uric Acid (blood)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Biomarkers</term>
<term>Uric Acid</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="radiography" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cohort Studies</term>
<term>Disease Progression</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Follow-Up Studies</term>
<term>Humans</term>
<term>Longitudinal Studies</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Predictive Value of Tests</term>
<term>Prospective Studies</term>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Context</title>
<p id="P1">Prospective epidemiological studies consistently indicate that Parkinson’s disease (PD) risk declines with increasing serum urate.</p>
</sec>
<sec id="S2"><title>Objective</title>
<p id="P2">To determine whether serum urate, a purine metabolite and potent antioxidant, predicts prognosis in PD.</p>
</sec>
<sec id="S3"><title>Design, Setting, and Participants</title>
<p id="P3">Prospective study among 804 subjects with early PD enrolled in the PRECEPT study, a clinical trial of the neuroprotectant potential of CEP-1347, conducted between April 2002 and August 2005 (average follow-up time 21.4 months).</p>
</sec>
<sec id="S4"><title>Main Outcome Measures</title>
<p id="P4">The primary study endpoint was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching endpoint according to quintiles of baseline serum urate, adjusting for gender, age and other potential covariates. Change in striatal uptake of [<sup>123</sup>
I]β-CIT, a marker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects.</p>
</sec>
<sec id="S5"><title>Results</title>
<p id="P5">The adjusted HR of reaching endpoint declined with increasing baseline concentrations of urate; subjects in the top quintile reached the endpoint at only half the rate of subjects in the bottom quintile (HR=0.51; 95% CI: 0.37 to 0.72; p=0.0002). This association was markedly stronger in men (HR=0.39; 95% CI: 0.26 to 0.60; p<0.0001) than in women (HR=0.77; 95% CI: 0.39 to 1.50; p=0.4). The percent loss in striatal [<sup>123</sup>
I]β-CIT uptake also improved with increasing serum urate concentrations (overall p for trend=0.002; men, p=0.0008; women, p= 0.4).</p>
</sec>
<sec id="S6"><title>Conclusion</title>
<p id="P6">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.</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list></list>
<tree><noCountry><name sortKey="Ascherio, Alberto" sort="Ascherio, Alberto" uniqKey="Ascherio A" first="Alberto" last="Ascherio">Alberto Ascherio</name>
<name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony" last="Lang">Anthony Lang</name>
<name sortKey="Marek, Kenneth" sort="Marek, Kenneth" uniqKey="Marek K" first="Kenneth" last="Marek">Kenneth Marek</name>
<name sortKey="Oakes, David" sort="Oakes, David" uniqKey="Oakes D" first="David" last="Oakes">David Oakes</name>
<name sortKey="Schwarzschild, Michael A" sort="Schwarzschild, Michael A" uniqKey="Schwarzschild M" first="Michael" last="Schwarzschild">Michael Schwarzschild</name>
<name sortKey="Schwid, Steven R" sort="Schwid, Steven R" uniqKey="Schwid S" first="Steven" last="Schwid">Steven Schwid</name>
<name sortKey="Shoulson, Ira" sort="Shoulson, Ira" uniqKey="Shoulson I" first="Ira" last="Shoulson">Ira Shoulson</name>
<name sortKey="Watts, Arthur" sort="Watts, Arthur" uniqKey="Watts A" first="Arthur" last="Watts">Arthur Watts</name>
</noCountry>
</tree>
</affiliations>
</record>
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