Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study
Identifieur interne : 000344 ( Main/Corpus ); précédent : 000343; suivant : 000345Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study
Auteurs : R. Nandhagopal ; L. Kuramoto ; M. Schulzer ; E. Mak ; J. Cragg ; Chong S. Lee ; J. Mckenzie ; S. Mccormick ; A. Samii ; A. Troiano ; T. J. Ruth ; V. Sossi ; R. De La Fuente-Fernandez ; Donald B. Calne ; A. J. StoesslSource :
- Brain [ 0006-8950 ] ; 2009-11.
Abstract
Parkinson's disease is a heterogeneous disorder with multiple factors contributing to disease initiation and progression. Using serial, multi-tracer positron emission tomography imaging, we studied a cohort of 78 subjects with sporadic Parkinson's disease to understand the disease course better. Subjects were scanned with radiotracers of presynaptic dopaminergic integrity at baseline and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses, using random effects, of the form BPND(t) or Kocc(t) ae(btdA) c, where BPND tracer binding potential (nondispaceable), KOCC tracer uptake constant a, b, c and d are regression parameters, t is the symptom duration and A is the age at onset, were utilized to model the longitudinal progression of radiotracer binding/uptake. We found that the initial tracer binding/uptake was significantly different in anterior versus posterior striatal subregions, indicating that the degree of denervation at disease onset was different between regions. However, the relative rate of decline in tracer binding/uptake was similar between the striatal subregions. While an antero-posterior gradient of severity was maintained for dopamine synthesis, storage and reuptake, the asymmetry between the more and less affected striatum became less prominent over the disease course. Our study suggests that the mechanisms underlying Parkinson's disease initiation and progression are probably different. Whereas factors responsible for disease initiation affect striatal subregions differently, those factors contributing to disease progression affect all striatal subregions to a similar degree and may therefore reflect non-specific mechanisms such as oxidative stress, inflammation or excitotoxicity.
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DOI: 10.1093/brain/awp209
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Nandhagopal</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="Kuramoto, L" sort="Kuramoto, L" uniqKey="Kuramoto L" first="L." last="Kuramoto">L. Kuramoto</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="Schulzer, M" sort="Schulzer, M" uniqKey="Schulzer M" first="M." last="Schulzer">M. Schulzer</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="Mak, E" sort="Mak, E" uniqKey="Mak E" first="E." last="Mak">E. Mak</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="Cragg, J" sort="Cragg, J" uniqKey="Cragg J" first="J." last="Cragg">J. Cragg</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 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>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="Mckenzie, J" sort="Mckenzie, J" uniqKey="Mckenzie J" first="J." last="Mckenzie">J. Mckenzie</name><affiliation><mods:affiliation>2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</mods:affiliation></affiliation></author><author><name sortKey="Mccormick, S" sort="Mccormick, S" uniqKey="Mccormick S" first="S." last="Mccormick">S. Mccormick</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="Samii, A" sort="Samii, A" uniqKey="Samii A" first="A." last="Samii">A. Samii</name><affiliation><mods:affiliation>2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</mods:affiliation></affiliation></author><author><name sortKey="Troiano, A" sort="Troiano, A" uniqKey="Troiano A" first="A." last="Troiano">A. Troiano</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="Ruth, T J" sort="Ruth, T J" uniqKey="Ruth T" first="T. J." last="Ruth">T. J. Ruth</name><affiliation><mods:affiliation>3 TRIUMF, Wesbrook Mall, Vancouver, BC V6T 2A3 Canada</mods:affiliation></affiliation></author><author><name sortKey="Sossi, V" sort="Sossi, V" uniqKey="Sossi V" first="V." last="Sossi">V. Sossi</name><affiliation><mods:affiliation>4 Department of Physics & Astronomy, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="De La Fuente Fernandez, R" sort="De La Fuente Fernandez, R" uniqKey="De La Fuente Fernandez R" first="R." last="De La Fuente-Fernandez">R. De La Fuente-Fernandez</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 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>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation></author><author><name sortKey="Stoessl, A J" sort="Stoessl, A J" uniqKey="Stoessl A" first="A. J." last="Stoessl">A. J. Stoessl</name><affiliation><mods:affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: jstoessl@interchange.ubc.ca</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-11">2009-11</date><biblScope unit="volume">132</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="2970">2970</biblScope><biblScope unit="page" to="2979">2979</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">54BBA92A9A3E58370CF3C12ED2373CE9525D23EB</idno><idno type="DOI">10.1093/brain/awp209</idno><idno type="ArticleID">awp209</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Parkinson's disease is a heterogeneous disorder with multiple factors contributing to disease initiation and progression. Using serial, multi-tracer positron emission tomography imaging, we studied a cohort of 78 subjects with sporadic Parkinson's disease to understand the disease course better. Subjects were scanned with radiotracers of presynaptic dopaminergic integrity at baseline and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses, using random effects, of the form BPND(t) or Kocc(t) ae(btdA) c, where BPND tracer binding potential (nondispaceable), KOCC tracer uptake constant a, b, c and d are regression parameters, t is the symptom duration and A is the age at onset, were utilized to model the longitudinal progression of radiotracer binding/uptake. We found that the initial tracer binding/uptake was significantly different in anterior versus posterior striatal subregions, indicating that the degree of denervation at disease onset was different between regions. However, the relative rate of decline in tracer binding/uptake was similar between the striatal subregions. While an antero-posterior gradient of severity was maintained for dopamine synthesis, storage and reuptake, the asymmetry between the more and less affected striatum became less prominent over the disease course. Our study suggests that the mechanisms underlying Parkinson's disease initiation and progression are probably different. Whereas factors responsible for disease initiation affect striatal subregions differently, those factors contributing to disease progression affect all striatal subregions to a similar degree and may therefore reflect non-specific mechanisms such as oxidative stress, inflammation or excitotoxicity.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>R. Nandhagopal</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>L. Kuramoto</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>M. Schulzer</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>E. Mak</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>J. Cragg</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>Chong S. Lee</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>J. McKenzie</name><affiliations><json:string>2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</json:string></affiliations></json:item><json:item><name>S. McCormick</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>A. Samii</name><affiliations><json:string>2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</json:string></affiliations></json:item><json:item><name>A. Troiano</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>T. J. Ruth</name><affiliations><json:string>3 TRIUMF, Wesbrook Mall, Vancouver, BC V6T 2A3 Canada</json:string></affiliations></json:item><json:item><name>V. Sossi</name><affiliations><json:string>4 Department of Physics & Astronomy, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>R. de la Fuente-Fernandez</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>Donald B. Calne</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string></affiliations></json:item><json:item><name>A. J. Stoessl</name><affiliations><json:string>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</json:string><json:string>E-mail: jstoessl@interchange.ubc.ca</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Original Articles</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PET</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>progression</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>asymmetry</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dopaminergic dysfunction</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Parkinson's disease is a heterogeneous disorder with multiple factors contributing to disease initiation and progression. Using serial, multi-tracer positron emission tomography imaging, we studied a cohort of 78 subjects with sporadic Parkinson's disease to understand the disease course better. Subjects were scanned with radiotracers of presynaptic dopaminergic integrity at baseline and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses, using random effects, of the form BPND(t) or Kocc(t) ae(btdA) c, where BPND tracer binding potential (nondispaceable), KOCC tracer uptake constant a, b, c and d are regression parameters, t is the symptom duration and A is the age at onset, were utilized to model the longitudinal progression of radiotracer binding/uptake. We found that the initial tracer binding/uptake was significantly different in anterior versus posterior striatal subregions, indicating that the degree of denervation at disease onset was different between regions. However, the relative rate of decline in tracer binding/uptake was similar between the striatal subregions. While an antero-posterior gradient of severity was maintained for dopamine synthesis, storage and reuptake, the asymmetry between the more and less affected striatum became less prominent over the disease course. Our study suggests that the mechanisms underlying Parkinson's disease initiation and progression are probably different. Whereas factors responsible for disease initiation affect striatal subregions differently, those factors contributing to disease progression affect all striatal subregions to a similar degree and may therefore reflect non-specific mechanisms such as oxidative stress, inflammation or excitotoxicity.</abstract><qualityIndicators><score>8.38</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612.68 x 790.866 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>6</keywordCount><abstractCharCount>1757</abstractCharCount><pdfWordCount>6267</pdfWordCount><pdfCharCount>40224</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>240</abstractWordCount></qualityIndicators><title>Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study</title><genre><json:string>research-article</json:string></genre><host><volume>132</volume><pages><last>2979</last><first>2970</first></pages><issn><json:string>0006-8950</json:string></issn><issue>11</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2156</json:string></eissn><title>Brain</title></host><categories><wos><json:string>CLINICAL NEUROLOGY</json:string><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1093/brain/awp209</json:string></doi><id>54BBA92A9A3E58370CF3C12ED2373CE9525D23EB</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/54BBA92A9A3E58370CF3C12ED2373CE9525D23EB/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/54BBA92A9A3E58370CF3C12ED2373CE9525D23EB/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/54BBA92A9A3E58370CF3C12ED2373CE9525D23EB/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>OUP</p></availability><date>2009-08-18</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study</title><author><persName><forename type="first">R.</forename><surname>Nandhagopal</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">L.</forename><surname>Kuramoto</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">M.</forename><surname>Schulzer</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">E.</forename><surname>Mak</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">J.</forename><surname>Cragg</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">Chong S.</forename><surname>Lee</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">J.</forename><surname>McKenzie</surname></persName><affiliation>2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</affiliation></author><author><persName><forename type="first">S.</forename><surname>McCormick</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">A.</forename><surname>Samii</surname></persName><affiliation>2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</affiliation></author><author><persName><forename type="first">A.</forename><surname>Troiano</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">T. J.</forename><surname>Ruth</surname></persName><affiliation>3 TRIUMF, Wesbrook Mall, Vancouver, BC V6T 2A3 Canada</affiliation></author><author><persName><forename type="first">V.</forename><surname>Sossi</surname></persName><affiliation>4 Department of Physics & Astronomy, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">R.</forename><surname>de la Fuente-Fernandez</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author><persName><forename type="first">Donald B.</forename><surname>Calne</surname></persName><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author><author corresp="yes"><persName><forename type="first">A. J.</forename><surname>Stoessl</surname></persName><email>jstoessl@interchange.ubc.ca</email><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation></author></analytic><monogr><title level="j">Brain</title><idno type="pISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-11"></date><biblScope unit="volume">132</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="2970">2970</biblScope><biblScope unit="page" to="2979">2979</biblScope></imprint></monogr><idno type="istex">54BBA92A9A3E58370CF3C12ED2373CE9525D23EB</idno><idno type="DOI">10.1093/brain/awp209</idno><idno type="ArticleID">awp209</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009-08-18</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Parkinson's disease is a heterogeneous disorder with multiple factors contributing to disease initiation and progression. Using serial, multi-tracer positron emission tomography imaging, we studied a cohort of 78 subjects with sporadic Parkinson's disease to understand the disease course better. Subjects were scanned with radiotracers of presynaptic dopaminergic integrity at baseline and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses, using random effects, of the form BPND(t) or Kocc(t) ae(btdA) c, where BPND tracer binding potential (nondispaceable), KOCC tracer uptake constant a, b, c and d are regression parameters, t is the symptom duration and A is the age at onset, were utilized to model the longitudinal progression of radiotracer binding/uptake. We found that the initial tracer binding/uptake was significantly different in anterior versus posterior striatal subregions, indicating that the degree of denervation at disease onset was different between regions. However, the relative rate of decline in tracer binding/uptake was similar between the striatal subregions. While an antero-posterior gradient of severity was maintained for dopamine synthesis, storage and reuptake, the asymmetry between the more and less affected striatum became less prominent over the disease course. Our study suggests that the mechanisms underlying Parkinson's disease initiation and progression are probably different. Whereas factors responsible for disease initiation affect striatal subregions differently, those factors contributing to disease progression affect all striatal subregions to a similar degree and may therefore reflect non-specific mechanisms such as oxidative stress, inflammation or excitotoxicity.</p></abstract><textClass><keywords scheme="keyword"><list><item><term>Original Articles</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>PET</term></item><item><term>progression</term></item><item><term>asymmetry</term></item><item><term>dopaminergic dysfunction</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-08-18">Created</change><change when="2009-11">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/54BBA92A9A3E58370CF3C12ED2373CE9525D23EB/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">brain</journal-id><journal-id journal-id-type="publisher-id">brainj</journal-id><journal-title>Brain</journal-title><issn pub-type="ppub">0006-8950</issn><issn pub-type="epub">1460-2156</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/brain/awp209</article-id><article-id pub-id-type="publisher-id">awp209</article-id><article-categories><subj-group><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Nandhagopal</surname><given-names>R.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kuramoto</surname><given-names>L.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schulzer</surname><given-names>M.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mak</surname><given-names>E.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cragg</surname><given-names>J.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Chong S.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>McKenzie</surname><given-names>J.</given-names></name><xref ref-type="aff" rid="AFF2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>McCormick</surname><given-names>S.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Samii</surname><given-names>A.</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Troiano</surname><given-names>A.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ruth</surname><given-names>T. J.</given-names></name><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sossi</surname><given-names>V.</given-names></name><xref ref-type="aff" rid="AFF4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>de la Fuente-Fernandez</surname><given-names>R.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Calne</surname><given-names>Donald B.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Stoessl</surname><given-names>A. J.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib></contrib-group><aff id="AFF1">1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</aff><aff id="AFF2">2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</aff><aff id="AFF3">3 TRIUMF, Wesbrook Mall, Vancouver, BC V6T 2A3 Canada</aff><aff id="AFF4">4 Department of Physics & Astronomy, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, Vancouver, BC V6T2B5 Canada</aff><author-notes><corresp>Correspondence to: A. Jon Stoessl, CM, MD, FRCPC, Pacific Parkinson's Research Centre, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC, V6T2B5 Canada E-mail: <email>jstoessl@interchange.ubc.ca</email></corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>18</day><month>8</month><year>2009</year></pub-date><volume>132</volume><issue>11</issue><fpage>2970</fpage><lpage>2979</lpage><history><date date-type="received"><day>24</day><month>1</month><year>2009</year></date><date date-type="rev-recd"><day>20</day><month>5</month><year>2009</year></date><date date-type="accepted"><day>26</day><month>6</month><year>2009</year></date></history><permissions><copyright-statement>© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement><copyright-year>2009</copyright-year></permissions><abstract><p>Parkinson's disease is a heterogeneous disorder with multiple factors contributing to disease initiation and progression. Using serial, multi-tracer positron emission tomography imaging, we studied a cohort of 78 subjects with sporadic Parkinson's disease to understand the disease course better. Subjects were scanned with radiotracers of presynaptic dopaminergic integrity at baseline and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses, using random effects, of the form BP<sub>ND</sub>(<italic>t</italic>) or <italic>K</italic><sub>occ</sub>(<italic>t</italic>) = <italic>a</italic>*<italic>e</italic><sup>(−</sup><italic><sup>bt</sup></italic><sup>−d</sup><italic><sup>A</sup></italic><sup>)</sup> + <italic>c</italic>, where BP<sub>ND</sub> = tracer binding potential (nondispaceable), K<sub>OCC</sub> = tracer uptake constant <italic>a</italic>, <italic>b</italic>, <italic>c</italic> and <italic>d</italic> are regression parameters, <italic>t</italic> is the symptom duration and <italic>A</italic> is the age at onset, were utilized to model the longitudinal progression of radiotracer binding/uptake. We found that the initial tracer binding/uptake was significantly different in anterior versus posterior striatal subregions, indicating that the degree of denervation at disease onset was different between regions. However, the relative rate of decline in tracer binding/uptake was similar between the striatal subregions. While an antero-posterior gradient of severity was maintained for dopamine synthesis, storage and reuptake, the asymmetry between the more and less affected striatum became less prominent over the disease course. Our study suggests that the mechanisms underlying Parkinson's disease initiation and progression are probably different. Whereas factors responsible for disease initiation affect striatal subregions differently, those factors contributing to disease progression affect all striatal subregions to a similar degree and may therefore reflect non-specific mechanisms such as oxidative stress, inflammation or excitotoxicity.</p></abstract><kwd-group><kwd>Parkinson's disease</kwd><kwd>PET</kwd><kwd>progression</kwd><kwd>asymmetry</kwd><kwd>dopaminergic dysfunction</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study</title></titleInfo><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Nandhagopal</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L.</namePart><namePart type="family">Kuramoto</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Schulzer</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E.</namePart><namePart type="family">Mak</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.</namePart><namePart type="family">Cragg</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chong S.</namePart><namePart type="family">Lee</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.</namePart><namePart type="family">McKenzie</namePart><affiliation>2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S.</namePart><namePart type="family">McCormick</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.</namePart><namePart type="family">Samii</namePart><affiliation>2 Department of Neurology, University of Washington, Seattle, WA 98195 USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.</namePart><namePart type="family">Troiano</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">T. J.</namePart><namePart type="family">Ruth</namePart><affiliation>3 TRIUMF, Wesbrook Mall, Vancouver, BC V6T 2A3 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">V.</namePart><namePart type="family">Sossi</namePart><affiliation>4 Department of Physics & Astronomy, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">de la Fuente-Fernandez</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Donald B.</namePart><namePart type="family">Calne</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">A. J.</namePart><namePart type="family">Stoessl</namePart><affiliation>1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada</affiliation><affiliation>E-mail: jstoessl@interchange.ubc.ca</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><topic>Original Articles</topic></subject><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2009-11</dateIssued><dateCreated encoding="w3cdtf">2009-08-18</dateCreated><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Parkinson's disease is a heterogeneous disorder with multiple factors contributing to disease initiation and progression. Using serial, multi-tracer positron emission tomography imaging, we studied a cohort of 78 subjects with sporadic Parkinson's disease to understand the disease course better. Subjects were scanned with radiotracers of presynaptic dopaminergic integrity at baseline and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses, using random effects, of the form BPND(t) or Kocc(t) ae(btdA) c, where BPND tracer binding potential (nondispaceable), KOCC tracer uptake constant a, b, c and d are regression parameters, t is the symptom duration and A is the age at onset, were utilized to model the longitudinal progression of radiotracer binding/uptake. We found that the initial tracer binding/uptake was significantly different in anterior versus posterior striatal subregions, indicating that the degree of denervation at disease onset was different between regions. However, the relative rate of decline in tracer binding/uptake was similar between the striatal subregions. While an antero-posterior gradient of severity was maintained for dopamine synthesis, storage and reuptake, the asymmetry between the more and less affected striatum became less prominent over the disease course. Our study suggests that the mechanisms underlying Parkinson's disease initiation and progression are probably different. Whereas factors responsible for disease initiation affect striatal subregions differently, those factors contributing to disease progression affect all striatal subregions to a similar degree and may therefore reflect non-specific mechanisms such as oxidative stress, inflammation or excitotoxicity.</abstract><subject><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>PET</topic><topic>progression</topic><topic>asymmetry</topic><topic>dopaminergic dysfunction</topic></subject><relatedItem type="host"><titleInfo><title>Brain</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0006-8950</identifier><identifier type="eISSN">1460-2156</identifier><identifier type="PublisherID">brainj</identifier><identifier type="PublisherID-hwp">brain</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>132</number></detail><detail type="issue"><caption>no.</caption><number>11</number></detail><extent unit="pages"><start>2970</start><end>2979</end></extent></part></relatedItem><identifier type="istex">54BBA92A9A3E58370CF3C12ED2373CE9525D23EB</identifier><identifier type="DOI">10.1093/brain/awp209</identifier><identifier type="ArticleID">awp209</identifier><accessCondition type="use and reproduction" contentType="copyright">The Author (2009). 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