Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications
Identifieur interne : 001044 ( Main/Corpus ); précédent : 001043; suivant : 001045Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications
Auteurs : Vesna Sossi ; Rau L De La Fuente-Ferna Ndez ; Michael Schulzer ; John Adams ; Jon StoesslSource :
- Brain [ 0006-8950 ] ; 2006-04.
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- KwdEn :
Abstract
Treatment-related motor complications in Parkinson's disease have been previously linked to disease-induced pre-synaptic alterations: dopaminergic denervation and changes in dopamine (DA) release patterns. The occurrence of such complications is also known to be partly dependent on the age of disease onset, occurring more frequently in patients with disease onset at a younger age. Using positron emission tomography (PET) and 4-h-long 18F-fluorodopa (FD) scans we have investigated in vivo an age dependence of disease-induced changes in DA turnover as a possible contributing factor to the age-related differences in treatment-related motor complications. We evaluated the relative changes in DA turnover (measured by its direct inverse, effective DA distribution volume—EDV) and DA synthesis and vesicular storage capacity (quantified by the plasma input uptake rate constant Ki) in Parkinson's disease patients as a function of age (n = 27, age range 38–79 years). After correcting for disease severity, a significant negative correlation was found between age and magnitude of disease-induced decrease in EDV and in Ki in the putamen (P < 0.001, P = 0.02, respectively). However, the difference between the disease-induced decrease in EDV and that in Ki also exhibited an age dependence (P < 0.001), indicating a relatively higher disease-induced increase in DA turnover (inverse of EDV) compared with the decrease in DA synthesis and storage rate in patients of younger age compared with older patients. This finding implies that DA turnover in younger-onset patients undergoes a relatively greater alteration and thus likely contributes to a greater imbalance between DA synthesis, storage and release, which could lead to larger swings in synaptic DA levels. It has indeed been suggested on theoretical grounds that such imbalance may contribute to the greater propensity for motor fluctuations. These results provide one possible explanation for the age-dependent occurrence of complications and support the existence of a pre-synaptic contribution to the occurrence of motor complications.
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DOI: 10.1093/brain/awl028
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ISTEX:002F98A4082AAD5FAFCC17DD395396D834365C29Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications</title><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation></author><author><name sortKey="De La Fuente Ferna Ndez, Rau L" sort="De La Fuente Ferna Ndez, Rau L" uniqKey="De La Fuente Ferna Ndez R" first="Rau L" last="De La Fuente-Ferna Ndez">Rau L De La Fuente-Ferna Ndez</name><affiliation><mods:affiliation>Division of Neurology, Hospital Arquitecto Marcide, 15405 Ferrol (A Coruña), Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation></author><author><name sortKey="Adams, John" sort="Adams, John" uniqKey="Adams J" first="John" last="Adams">John Adams</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, Vancouver, Canada and</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation></author><author><name sortKey="Stoessl, Jon" sort="Stoessl, Jon" uniqKey="Stoessl J" first="Jon" last="Stoessl">Jon Stoessl</name><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British 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L" sort="De La Fuente Ferna Ndez, Rau L" uniqKey="De La Fuente Ferna Ndez R" first="Rau L" last="De La Fuente-Ferna Ndez">Rau L De La Fuente-Ferna Ndez</name><affiliation><mods:affiliation>Division of Neurology, Hospital Arquitecto Marcide, 15405 Ferrol (A Coruña), Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation></author><author><name sortKey="Adams, John" sort="Adams, John" uniqKey="Adams J" first="John" last="Adams">John Adams</name><affiliation><mods:affiliation>Pacific Parkinson's Research Centre, Vancouver, Canada and</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation></author><author><name sortKey="Stoessl, Jon" sort="Stoessl, Jon" uniqKey="Stoessl J" first="Jon" last="Stoessl">Jon Stoessl</name><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation><affiliation><mods:affiliation>University of British Columbia,</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><title level="j" type="abbrev">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2006-04">2006-04</date><biblScope unit="volume">129</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="1050">1050</biblScope><biblScope unit="page" to="1058">1058</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">002F98A4082AAD5FAFCC17DD395396D834365C29</idno><idno type="DOI">10.1093/brain/awl028</idno><idno type="local">awl028</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>18F-DA = 18F-fluorodopamine</term><term>3OMFD = 3-O-methylfluorodopa</term><term>DA = dopamine</term><term>DA turnover</term><term>EDV = effective DA distribution volume</term><term>FD = 18F-fluorodopa</term><term>Ki = FD uptake rate constant</term><term>PET = positron emission tomography</term><term>ROIs = regions of interest</term><term>age dependence</term><term>dopaminergic system</term><term>motor complications</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Treatment-related motor complications in Parkinson's disease have been previously linked to disease-induced pre-synaptic alterations: dopaminergic denervation and changes in dopamine (DA) release patterns. The occurrence of such complications is also known to be partly dependent on the age of disease onset, occurring more frequently in patients with disease onset at a younger age. Using positron emission tomography (PET) and 4-h-long 18F-fluorodopa (FD) scans we have investigated in vivo an age dependence of disease-induced changes in DA turnover as a possible contributing factor to the age-related differences in treatment-related motor complications. We evaluated the relative changes in DA turnover (measured by its direct inverse, effective DA distribution volume—EDV) and DA synthesis and vesicular storage capacity (quantified by the plasma input uptake rate constant Ki) in Parkinson's disease patients as a function of age (n = 27, age range 38–79 years). After correcting for disease severity, a significant negative correlation was found between age and magnitude of disease-induced decrease in EDV and in Ki in the putamen (P < 0.001, P = 0.02, respectively). However, the difference between the disease-induced decrease in EDV and that in Ki also exhibited an age dependence (P < 0.001), indicating a relatively higher disease-induced increase in DA turnover (inverse of EDV) compared with the decrease in DA synthesis and storage rate in patients of younger age compared with older patients. This finding implies that DA turnover in younger-onset patients undergoes a relatively greater alteration and thus likely contributes to a greater imbalance between DA synthesis, storage and release, which could lead to larger swings in synaptic DA levels. It has indeed been suggested on theoretical grounds that such imbalance may contribute to the greater propensity for motor fluctuations. These results provide one possible explanation for the age-dependent occurrence of complications and support the existence of a pre-synaptic contribution to the occurrence of motor complications.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Vesna Sossi</name><affiliations><json:string>University of British Columbia,</json:string><json:string>University of British Columbia,</json:string></affiliations></json:item><json:item><name>Raúl de la Fuente-Fernández</name><affiliations><json:string>Division of Neurology, Hospital Arquitecto Marcide, 15405 Ferrol (A Coruña), Spain</json:string><json:string>University of British Columbia,</json:string></affiliations></json:item><json:item><name>Michael Schulzer</name><affiliations><json:string>University of British Columbia,</json:string><json:string>University of British Columbia,</json:string></affiliations></json:item><json:item><name>John Adams</name><affiliations><json:string>Pacific Parkinson's Research Centre, Vancouver, Canada and</json:string><json:string>University of British Columbia,</json:string></affiliations></json:item><json:item><name>Jon Stoessl</name><affiliations><json:string>University of British Columbia,</json:string><json:string>University of British Columbia,</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>dopaminergic system</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DA turnover</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>motor complications</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>age dependence</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DA = dopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>EDV = effective DA distribution volume</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>FD = 18F-fluorodopa</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>18F-DA = 18F-fluorodopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Ki = FD uptake rate constant</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>3OMFD = 3-O-methylfluorodopa</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PET = positron emission tomography</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ROIs = regions of interest</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Treatment-related motor complications in Parkinson's disease have been previously linked to disease-induced pre-synaptic alterations: dopaminergic denervation and changes in dopamine (DA) release patterns. The occurrence of such complications is also known to be partly dependent on the age of disease onset, occurring more frequently in patients with disease onset at a younger age. Using positron emission tomography (PET) and 4-h-long 18F-fluorodopa (FD) scans we have investigated in vivo an age dependence of disease-induced changes in DA turnover as a possible contributing factor to the age-related differences in treatment-related motor complications. We evaluated the relative changes in DA turnover (measured by its direct inverse, effective DA distribution volume—EDV) and DA synthesis and vesicular storage capacity (quantified by the plasma input uptake rate constant Ki) in Parkinson's disease patients as a function of age (n = 27, age range 38–79 years). After correcting for disease severity, a significant negative correlation was found between age and magnitude of disease-induced decrease in EDV and in Ki in the putamen (P > 0.001, P = 0.02, respectively). However, the difference between the disease-induced decrease in EDV and that in Ki also exhibited an age dependence (P > 0.001), indicating a relatively higher disease-induced increase in DA turnover (inverse of EDV) compared with the decrease in DA synthesis and storage rate in patients of younger age compared with older patients. This finding implies that DA turnover in younger-onset patients undergoes a relatively greater alteration and thus likely contributes to a greater imbalance between DA synthesis, storage and release, which could lead to larger swings in synaptic DA levels. It has indeed been suggested on theoretical grounds that such imbalance may contribute to the greater propensity for motor fluctuations. These results provide one possible explanation for the age-dependent occurrence of complications and support the existence of a pre-synaptic contribution to the occurrence of motor complications.</abstract><qualityIndicators><score>8.5</score><pdfVersion>1.4</pdfVersion><pdfPageSize>624.307 x 804.307 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>13</keywordCount><abstractCharCount>2101</abstractCharCount><pdfWordCount>5545</pdfWordCount><pdfCharCount>35162</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>308</abstractWordCount></qualityIndicators><title>Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications</title><genre><json:string>research-article</json:string></genre><host><volume>129</volume><pages><last>1058</last><first>1050</first></pages><issn><json:string>0006-8950</json:string></issn><issue>4</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>2006</publicationDate><copyrightDate>2006</copyrightDate><doi><json:string>10.1093/brain/awl028</json:string></doi><id>002F98A4082AAD5FAFCC17DD395396D834365C29</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/002F98A4082AAD5FAFCC17DD395396D834365C29/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/002F98A4082AAD5FAFCC17DD395396D834365C29/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/002F98A4082AAD5FAFCC17DD395396D834365C29/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>OUP</p></availability><date>2006-02-13</date></publicationStmt><notesStmt><note>Correspondence to: Vesna Sossi, PhD, Pacific Parkinson's Research Centre, Room M37, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, Canada BC V6T 2B5 E-mail: vesna@physics.ubc.ca</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications</title><author><persName><forename type="first">Vesna</forename><surname>Sossi</surname></persName><affiliation>University of British Columbia,</affiliation><affiliation>University of British Columbia,</affiliation></author><author><persName><forename type="first">Raúl</forename><surname>de la Fuente-Fernández</surname></persName><affiliation>Division of Neurology, Hospital Arquitecto Marcide, 15405 Ferrol (A Coruña), Spain</affiliation><affiliation>University of British Columbia,</affiliation></author><author><persName><forename type="first">Michael</forename><surname>Schulzer</surname></persName><affiliation>University of British Columbia,</affiliation><affiliation>University of British Columbia,</affiliation></author><author><persName><forename type="first">John</forename><surname>Adams</surname></persName><affiliation>Pacific Parkinson's Research Centre, Vancouver, Canada and</affiliation><affiliation>University of British Columbia,</affiliation></author><author><persName><forename type="first">Jon</forename><surname>Stoessl</surname></persName><affiliation>University of British Columbia,</affiliation><affiliation>University of British Columbia,</affiliation></author></analytic><monogr><title level="j">Brain</title><title level="j" type="abbrev">Brain</title><idno type="pISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2006-04"></date><biblScope unit="volume">129</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="1050">1050</biblScope><biblScope unit="page" to="1058">1058</biblScope></imprint></monogr><idno type="istex">002F98A4082AAD5FAFCC17DD395396D834365C29</idno><idno type="DOI">10.1093/brain/awl028</idno><idno type="local">awl028</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2006-02-13</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Treatment-related motor complications in Parkinson's disease have been previously linked to disease-induced pre-synaptic alterations: dopaminergic denervation and changes in dopamine (DA) release patterns. The occurrence of such complications is also known to be partly dependent on the age of disease onset, occurring more frequently in patients with disease onset at a younger age. Using positron emission tomography (PET) and 4-h-long 18F-fluorodopa (FD) scans we have investigated in vivo an age dependence of disease-induced changes in DA turnover as a possible contributing factor to the age-related differences in treatment-related motor complications. We evaluated the relative changes in DA turnover (measured by its direct inverse, effective DA distribution volume—EDV) and DA synthesis and vesicular storage capacity (quantified by the plasma input uptake rate constant Ki) in Parkinson's disease patients as a function of age (n = 27, age range 38–79 years). After correcting for disease severity, a significant negative correlation was found between age and magnitude of disease-induced decrease in EDV and in Ki in the putamen (P < 0.001, P = 0.02, respectively). However, the difference between the disease-induced decrease in EDV and that in Ki also exhibited an age dependence (P < 0.001), indicating a relatively higher disease-induced increase in DA turnover (inverse of EDV) compared with the decrease in DA synthesis and storage rate in patients of younger age compared with older patients. This finding implies that DA turnover in younger-onset patients undergoes a relatively greater alteration and thus likely contributes to a greater imbalance between DA synthesis, storage and release, which could lead to larger swings in synaptic DA levels. It has indeed been suggested on theoretical grounds that such imbalance may contribute to the greater propensity for motor fluctuations. These results provide one possible explanation for the age-dependent occurrence of complications and support the existence of a pre-synaptic contribution to the occurrence of motor complications.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>KWD</head><item><term>dopaminergic system</term></item><item><term>DA turnover</term></item><item><term>motor complications</term></item><item><term>age dependence</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>ABR</head><item><term>DA = dopamine</term></item><item><term>EDV = effective DA distribution volume</term></item><item><term>FD = 18F-fluorodopa</term></item><item><term>18F-DA = 18F-fluorodopamine</term></item><item><term>Ki = FD uptake rate constant</term></item><item><term>3OMFD = 3-O-methylfluorodopa</term></item><item><term>PET = positron emission tomography</term></item><item><term>ROIs = regions of interest</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-02-13">Created</change><change when="2006-04">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/002F98A4082AAD5FAFCC17DD395396D834365C29/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="US-ASCII"</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 xml:lang="en" article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">brain</journal-id><journal-id journal-id-type="nlm-ta">Brain</journal-id><journal-id journal-id-type="publisher-id">brainj</journal-id><journal-title>Brain</journal-title><abbrev-journal-title abbrev-type="publisher">Brain</abbrev-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="other">awl028</article-id><article-id pub-id-type="doi">10.1093/brain/awl028</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sossi</surname><given-names>Vesna</given-names></name><xref rid="AFF1">1</xref></contrib><contrib contrib-type="author"><name><surname>de la Fuente-Fernández</surname><given-names>Raúl</given-names></name><xref rid="AFF3">3</xref></contrib><contrib contrib-type="author"><name><surname>Schulzer</surname><given-names>Michael</given-names></name><xref rid="AFF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Adams</surname><given-names>John</given-names></name><xref rid="AFF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Stoessl</surname><given-names>Jon</given-names></name><xref rid="AFF1">1</xref><xref rid="AFF2">2</xref></contrib><aff><target target-type="aff" id="AFF1"></target><label>1</label>University of British Columbia, <target target-type="aff" id="AFF2"></target><label>2</label>Pacific Parkinson's Research Centre, Vancouver, Canada and <target target-type="aff" id="AFF3"></target><label>3</label>Division of Neurology, Hospital Arquitecto Marcide, 15405 Ferrol (A Coruña), Spain</aff></contrib-group><author-notes><corresp>Correspondence to: Vesna Sossi, PhD, Pacific Parkinson's Research Centre, Room M37, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, Canada BC V6T 2B5 E-mail: <ext-link xlink:href="vesna@physics.ubc.ca" ext-link-type="email">vesna@physics.ubc.ca</ext-link></corresp></author-notes><pub-date pub-type="ppub"><month>April</month><year>2006</year></pub-date><pub-date pub-type="epub"><day>13</day><month>2</month><year>2006</year></pub-date><volume>129</volume><issue>4</issue><fpage>1050</fpage><lpage>1058</lpage><history><date date-type="accepted"><day>12</day><month>1</month><year>2006</year></date><date date-type="received"><day>28</day><month>7</month><year>2005</year></date><date date-type="rev-recd"><day>6</day><month>1</month><year>2006</year></date></history><copyright-statement>© The Author (2006). 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>2006</copyright-year><abstract xml:lang="en"><p>Treatment-related motor complications in Parkinson's disease have been previously linked to disease-induced pre-synaptic alterations: dopaminergic denervation and changes in dopamine (DA) release patterns. The occurrence of such complications is also known to be partly dependent on the age of disease onset, occurring more frequently in patients with disease onset at a younger age. Using positron emission tomography (PET) and 4-h-long <sup>18</sup>F-fluorodopa (FD) scans we have investigated <italic>in vivo</italic> an age dependence of disease-induced changes in DA turnover as a possible contributing factor to the age-related differences in treatment-related motor complications. We evaluated the relative changes in DA turnover (measured by its direct inverse, effective DA distribution volume—EDV) and DA synthesis and vesicular storage capacity (quantified by the plasma input uptake rate constant <italic>K<sub>i</sub></italic>) in Parkinson's disease patients as a function of age (<italic>n</italic> = 27, age range 38–79 years). After correcting for disease severity, a significant negative correlation was found between age and magnitude of disease-induced decrease in EDV and in <italic>K<sub>i</sub></italic> in the putamen (<italic>P</italic> < 0.001, <italic>P</italic> = 0.02, respectively). However, the difference between the disease-induced decrease in EDV and that in <italic>K<sub>i</sub></italic> also exhibited an age dependence (<italic>P</italic> < 0.001), indicating a relatively higher disease-induced increase in DA turnover (inverse of EDV) compared with the decrease in DA synthesis and storage rate in patients of younger age compared with older patients. This finding implies that DA turnover in younger-onset patients undergoes a relatively greater alteration and thus likely contributes to a greater imbalance between DA synthesis, storage and release, which could lead to larger swings in synaptic DA levels. It has indeed been suggested on theoretical grounds that such imbalance may contribute to the greater propensity for motor fluctuations. These results provide one possible explanation for the age-dependent occurrence of complications and support the existence of a pre-synaptic contribution to the occurrence of motor complications.</p></abstract><kwd-group kwd-group-type="KWD" xml:lang="en"><kwd>dopaminergic system</kwd><kwd>DA turnover</kwd><kwd>motor complications</kwd><kwd>age dependence</kwd></kwd-group><kwd-group kwd-group-type="ABR" xml:lang="en"><kwd>DA = dopamine</kwd><kwd>EDV = effective DA distribution volume</kwd><kwd>FD = <sup>18</sup>F-fluorodopa</kwd><kwd><sup>18</sup>F-DA = <sup>18</sup>F-fluorodopamine</kwd><kwd><italic>K</italic><sub>i</sub> = FD uptake rate constant</kwd><kwd>3OMFD = 3-<italic>O</italic>-methylfluorodopa</kwd><kwd>PET = positron emission tomography</kwd><kwd>ROIs = regions of interest</kwd></kwd-group><custom-meta-wrap><custom-meta><meta-name>hwp-legacy-fpage</meta-name><meta-value>1050</meta-value></custom-meta><custom-meta><meta-name>cover-date</meta-name><meta-value>April 2006</meta-value></custom-meta><custom-meta><meta-name>hwp-legacy-dochead</meta-name><meta-value>Original Article</meta-value></custom-meta></custom-meta-wrap></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications</title></titleInfo><name type="personal"><namePart type="given">Vesna</namePart><namePart type="family">Sossi</namePart><affiliation>University of British Columbia,</affiliation><affiliation>University of British Columbia,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Raúl</namePart><namePart type="family">de la Fuente-Fernández</namePart><affiliation>Division of Neurology, Hospital Arquitecto Marcide, 15405 Ferrol (A Coruña), Spain</affiliation><affiliation>University of British Columbia,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Schulzer</namePart><affiliation>University of British Columbia,</affiliation><affiliation>University of British Columbia,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John</namePart><namePart type="family">Adams</namePart><affiliation>Pacific Parkinson's Research Centre, Vancouver, Canada and</affiliation><affiliation>University of British Columbia,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jon</namePart><namePart type="family">Stoessl</namePart><affiliation>University of British Columbia,</affiliation><affiliation>University of British Columbia,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2006-04</dateIssued><dateCreated encoding="w3cdtf">2006-02-13</dateCreated><copyrightDate encoding="w3cdtf">2006</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 lang="en">Treatment-related motor complications in Parkinson's disease have been previously linked to disease-induced pre-synaptic alterations: dopaminergic denervation and changes in dopamine (DA) release patterns. The occurrence of such complications is also known to be partly dependent on the age of disease onset, occurring more frequently in patients with disease onset at a younger age. Using positron emission tomography (PET) and 4-h-long 18F-fluorodopa (FD) scans we have investigated in vivo an age dependence of disease-induced changes in DA turnover as a possible contributing factor to the age-related differences in treatment-related motor complications. We evaluated the relative changes in DA turnover (measured by its direct inverse, effective DA distribution volume—EDV) and DA synthesis and vesicular storage capacity (quantified by the plasma input uptake rate constant Ki) in Parkinson's disease patients as a function of age (n = 27, age range 38–79 years). After correcting for disease severity, a significant negative correlation was found between age and magnitude of disease-induced decrease in EDV and in Ki in the putamen (P < 0.001, P = 0.02, respectively). However, the difference between the disease-induced decrease in EDV and that in Ki also exhibited an age dependence (P < 0.001), indicating a relatively higher disease-induced increase in DA turnover (inverse of EDV) compared with the decrease in DA synthesis and storage rate in patients of younger age compared with older patients. This finding implies that DA turnover in younger-onset patients undergoes a relatively greater alteration and thus likely contributes to a greater imbalance between DA synthesis, storage and release, which could lead to larger swings in synaptic DA levels. It has indeed been suggested on theoretical grounds that such imbalance may contribute to the greater propensity for motor fluctuations. These results provide one possible explanation for the age-dependent occurrence of complications and support the existence of a pre-synaptic contribution to the occurrence of motor complications.</abstract><note type="author-notes">Correspondence to: Vesna Sossi, PhD, Pacific Parkinson's Research Centre, Room M37, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, Canada BC V6T 2B5 E-mail: vesna@physics.ubc.ca</note><subject lang="en"><genre>KWD</genre><topic>dopaminergic system</topic><topic>DA turnover</topic><topic>motor complications</topic><topic>age dependence</topic></subject><subject lang="en"><genre>ABR</genre><topic>DA = dopamine</topic><topic>EDV = effective DA distribution volume</topic><topic>FD = 18F-fluorodopa</topic><topic>18F-DA = 18F-fluorodopamine</topic><topic>Ki = FD uptake rate constant</topic><topic>3OMFD = 3-O-methylfluorodopa</topic><topic>PET = positron emission tomography</topic><topic>ROIs = regions of interest</topic></subject><relatedItem type="host"><titleInfo><title>Brain</title></titleInfo><titleInfo type="abbreviated"><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><identifier type="PublisherID-nlm-ta">Brain</identifier><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>129</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>1050</start><end>1058</end></extent></part></relatedItem><identifier type="istex">002F98A4082AAD5FAFCC17DD395396D834365C29</identifier><identifier type="DOI">10.1093/brain/awl028</identifier><identifier type="local">awl028</identifier><accessCondition type="use and reproduction" contentType="copyright">© The Author (2006). 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