Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease
Identifieur interne : 000369 ( Main/Corpus ); précédent : 000368; suivant : 000370Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease
Auteurs : Raúl De La Fuente-Fernández ; Michael Schulzer ; Lisa Kuramoto ; Jacquelyn Cragg ; Nandhagopal Ramachandiran ; Wing L. Au ; Edwin Mak ; Jess Mckenzie ; Siobhan Mccormick ; Vesna Sossi ; Thomas J. Ruth ; Chong S. Lee ; Donald B. Calne ; A. Jon StoesslSource :
- Annals of Neurology [ 0364-5134 ] ; 2011-05.
Abstract
Objective:: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods:: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d‐threo‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐[18F]‐fluoro‐L‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase. Results:: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p < 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation:: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011;
Url:
DOI: 10.1002/ana.22284
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Au</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Mak, Edwin" sort="Mak, Edwin" uniqKey="Mak E" first="Edwin" last="Mak">Edwin Mak</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Mckenzie, Jess" sort="Mckenzie, Jess" uniqKey="Mckenzie J" first="Jess" last="Mckenzie">Jess Mckenzie</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Mccormick, Siobhan" sort="Mccormick, Siobhan" uniqKey="Mccormick S" first="Siobhan" last="Mccormick">Siobhan Mccormick</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation><mods:affiliation>Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><affiliation><mods:affiliation>TRIUMF, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Lee, Chong S" sort="Lee, Chong S" uniqKey="Lee C" first="Chong S." last="Lee">Chong S. Lee</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Calne, Donald B" sort="Calne, Donald B" uniqKey="Calne D" first="Donald B." last="Calne">Donald B. Calne</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-05">2011-05</date><biblScope unit="volume">69</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="803">803</biblScope><biblScope unit="page" to="810">810</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">E02D1CF0A2675938DABC1F708869227D8EA17ED8</idno><idno type="DOI">10.1002/ana.22284</idno><idno type="ArticleID">ANA22284</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective:: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods:: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d‐threo‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐[18F]‐fluoro‐L‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase. Results:: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p < 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation:: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011;</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Raúl de la Fuente‐Fernández MD, FRCPC</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Michael Schulzer MD, PhD</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Lisa Kuramoto MSc</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Jacquelyn Cragg BSc</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Nandhagopal Ramachandiran MD</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Wing L. Au MD</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Edwin Mak BASc</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Jess McKenzie LPN</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Siobhan McCormick MSc</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Vesna Sossi PhD</name><affiliations><json:string>Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Thomas J. Ruth PhD</name><affiliations><json:string>TRIUMF, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Chong S. Lee MD</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Donald B. Calne DM</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>A. Jon Stoessl MD, FRCPC</name><affiliations><json:string>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item></author><articleId><json:string>ANA22284</json:string></articleId><language><json:string>eng</json:string></language><abstract>Objective:: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods:: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d‐threo‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐[18F]‐fluoro‐L‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase. Results:: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p > 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation:: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011;</abstract><qualityIndicators><score>7.085</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 801 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1403</abstractCharCount><pdfWordCount>4649</pdfWordCount><pdfCharCount>30459</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>203</abstractWordCount></qualityIndicators><title>Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease</title><genre><json:string>article</json:string></genre><host><volume>69</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>8</total><last>810</last><first>803</first></pages><issn><json:string>0364-5134</json:string></issn><issue>5</issue><subject><json:item><value>Original Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8249</json:string></eissn><title>Annals of Neurology</title><doi><json:string>10.1002/(ISSN)1531-8249</json:string></doi></host><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1002/ana.22284</json:string></doi><id>E02D1CF0A2675938DABC1F708869227D8EA17ED8</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/E02D1CF0A2675938DABC1F708869227D8EA17ED8/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/E02D1CF0A2675938DABC1F708869227D8EA17ED8/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/E02D1CF0A2675938DABC1F708869227D8EA17ED8/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2011</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease</title><author><persName><forename type="first">Raúl</forename><surname>de la Fuente‐Fernández</surname></persName><roleName type="degree">MD, FRCPC</roleName><note type="correspondence"><p>Correspondence: Pacific Parkinson's Research Centre, University of British Columbia, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5</p></note><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Michael</forename><surname>Schulzer</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Lisa</forename><surname>Kuramoto</surname></persName><roleName type="degree">MSc</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Jacquelyn</forename><surname>Cragg</surname></persName><roleName type="degree">BSc</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Nandhagopal</forename><surname>Ramachandiran</surname></persName><roleName type="degree">MD</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Wing L.</forename><surname>Au</surname></persName><roleName type="degree">MD</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Edwin</forename><surname>Mak</surname></persName><roleName type="degree">BASc</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Jess</forename><surname>McKenzie</surname></persName><roleName type="degree">LPN</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Siobhan</forename><surname>McCormick</surname></persName><roleName type="degree">MSc</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Vesna</forename><surname>Sossi</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Thomas J.</forename><surname>Ruth</surname></persName><roleName type="degree">PhD</roleName><affiliation>TRIUMF, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Chong S.</forename><surname>Lee</surname></persName><roleName type="degree">MD</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">Donald B.</forename><surname>Calne</surname></persName><roleName type="degree">DM</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">A. Jon</forename><surname>Stoessl</surname></persName><roleName type="degree">MD, FRCPC</roleName><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-05"></date><biblScope unit="volume">69</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="803">803</biblScope><biblScope unit="page" to="810">810</biblScope></imprint></monogr><idno type="istex">E02D1CF0A2675938DABC1F708869227D8EA17ED8</idno><idno type="DOI">10.1002/ana.22284</idno><idno type="ArticleID">ANA22284</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Objective:: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods:: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d‐threo‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐[18F]‐fluoro‐L‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase. Results:: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p < 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation:: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. 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number="8"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="publisher">Copyright © 2011 American Neurological Association</copyright><eventGroup><event type="manuscriptReceived" date="2010-06-17"></event><event type="manuscriptRevised" date="2010-08-18"></event><event type="manuscriptAccepted" date="2010-09-24"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.4.8 mode:FullText" date="2011-04-22"></event><event type="publishedOnlineAccepted" date="2010-10-28"></event><event type="publishedOnlineEarlyUnpaginated" date="2011-01-18"></event><event type="firstOnline" date="2011-01-18"></event><event type="publishedOnlineFinalForm" date="2011-04-22"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-03"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">803</numbering><numbering type="pageLast">810</numbering></numberingGroup><correspondenceTo>Pacific Parkinson's Research Centre, University of British Columbia, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA22284.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="4"></count><count type="referenceTotal" number="45"></count><count type="wordTotal" number="5227"></count></countGroup><titleGroup><title type="main" xml:lang="en">Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease</title><title type="short" xml:lang="en">Nigrostriatal Dysfunction in Parkinson's Disease</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Raúl</givenNames><familyName>de la Fuente‐Fernández</familyName><degrees>MD, FRCPC</degrees></personName><contactDetails><email>raulff@interchange.ubc.ca</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Michael</givenNames><familyName>Schulzer</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Lisa</givenNames><familyName>Kuramoto</familyName><degrees>MSc</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Jacquelyn</givenNames><familyName>Cragg</familyName><degrees>BSc</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Nandhagopal</givenNames><familyName>Ramachandiran</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Wing L.</givenNames><familyName>Au</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Edwin</givenNames><familyName>Mak</familyName><degrees>BASc</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Jess</givenNames><familyName>McKenzie</familyName><degrees>LPN</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Siobhan</givenNames><familyName>McCormick</familyName><degrees>MSc</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Vesna</givenNames><familyName>Sossi</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Thomas J.</givenNames><familyName>Ruth</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Chong S.</givenNames><familyName>Lee</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Donald B.</givenNames><familyName>Calne</familyName><degrees>DM</degrees></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af1"><personName><givenNames>A. Jon</givenNames><familyName>Stoessl</familyName><degrees>MD, FRCPC</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="CA" type="organization"><unparsedAffiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="CA" type="organization"><unparsedAffiliation>Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="CA" type="organization"><unparsedAffiliation>TRIUMF, Vancouver, BC, Canada</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main">Objective:</title><p>To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD).</p></section><section xml:id="abs1-2"><title type="main">Methods:</title><p>PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [<sup>11</sup>C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [<sup>11</sup>C]d‐<i>threo</i>‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐[<sup>18</sup>F]‐fluoro‐<sc>L</sc>‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase.</p></section><section xml:id="abs1-3"><title type="main">Results:</title><p>The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (<i>p</i> = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (<i>p</i> <i><</i> 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients.</p></section><section xml:id="abs1-4"><title type="main">Interpretation:</title><p>Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011;</p></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Nigrostriatal Dysfunction in Parkinson's Disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Raúl</namePart><namePart type="family">de la Fuente‐Fernández</namePart><namePart type="termsOfAddress">MD, FRCPC</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><description>Correspondence: Pacific Parkinson's Research Centre, University of British Columbia, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Schulzer</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lisa</namePart><namePart type="family">Kuramoto</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jacquelyn</namePart><namePart type="family">Cragg</namePart><namePart type="termsOfAddress">BSc</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nandhagopal</namePart><namePart type="family">Ramachandiran</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wing L.</namePart><namePart type="family">Au</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Edwin</namePart><namePart type="family">Mak</namePart><namePart type="termsOfAddress">BASc</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jess</namePart><namePart type="family">McKenzie</namePart><namePart type="termsOfAddress">LPN</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Siobhan</namePart><namePart type="family">McCormick</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vesna</namePart><namePart type="family">Sossi</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas J.</namePart><namePart type="family">Ruth</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>TRIUMF, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chong S.</namePart><namePart type="family">Lee</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Donald B.</namePart><namePart type="family">Calne</namePart><namePart type="termsOfAddress">DM</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A. Jon</namePart><namePart type="family">Stoessl</namePart><namePart type="termsOfAddress">MD, FRCPC</namePart><affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-05</dateIssued><dateCaptured encoding="w3cdtf">2010-06-17</dateCaptured><dateValid encoding="w3cdtf">2010-09-24</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">4</extent><extent unit="references">45</extent><extent unit="words">5227</extent></physicalDescription><abstract lang="en">Objective:: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods:: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d‐threo‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐[18F]‐fluoro‐L‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase. Results:: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p < 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation:: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011;</abstract><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>69</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>803</start><end>810</end><total>8</total></extent></part></relatedItem><identifier type="istex">E02D1CF0A2675938DABC1F708869227D8EA17ED8</identifier><identifier type="DOI">10.1002/ana.22284</identifier><identifier type="ArticleID">ANA22284</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2011 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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