Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications.
Identifieur interne : 000618 ( Ncbi/Merge ); précédent : 000617; suivant : 000619Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications.
Auteurs : Vesna Sossi [Canada] ; Raúl De La Fuente-Fernández ; Michael Schulzer ; John Adams ; Jon StoesslSource :
- Brain : a journal of neurology [ 1460-2156 ] ; 2006.
English descriptors
- KwdEn :
- Adult, Age Factors, Age of Onset, Aged, Antiparkinson Agents (adverse effects), Antiparkinson Agents (blood), Dihydroxyphenylalanine (analogs & derivatives), Dopamine Agents (adverse effects), Dopamine Agents (blood), Dyskinesia, Drug-Induced (blood), Dyskinesia, Drug-Induced (etiology), Female, Humans, Levodopa (adverse effects), Levodopa (blood), Male, Middle Aged, Parkinson Disease (blood), Parkinson Disease (diagnostic imaging), Parkinson Disease (drug therapy), Tomography, Emission-Computed.
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Dopamine Agents, Levodopa.
- chemical , analogs & derivatives : Dihydroxyphenylalanine.
- chemical , blood : Antiparkinson Agents, Dopamine Agents, Levodopa.
- blood : Dyskinesia, Drug-Induced, Parkinson Disease.
- diagnostic imaging : Parkinson Disease.
- drug therapy : Parkinson Disease.
- etiology : Dyskinesia, Drug-Induced.
- Adult, Age Factors, Age of Onset, Aged, Female, Humans, Male, Middle Aged, Tomography, Emission-Computed.
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.
DOI: 10.1093/brain/awl028
PubMed: 16476675
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John" sort="Adams, John" uniqKey="Adams J" first="John" last="Adams">John Adams</name></author><author><name sortKey="Stoessl, Jon" sort="Stoessl, Jon" uniqKey="Stoessl J" first="Jon" last="Stoessl">Jon Stoessl</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="RBID">pubmed:16476675</idno><idno type="pmid">16476675</idno><idno type="doi">10.1093/brain/awl028</idno><idno type="wicri:Area/PubMed/Corpus">001177</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001177</idno><idno type="wicri:Area/PubMed/Curation">001177</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001177</idno><idno type="wicri:Area/PubMed/Checkpoint">001177</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001177</idno><idno type="wicri:Area/Ncbi/Merge">000618</idno></publicationStmt><sourceDesc><biblStruct><analytic><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 wicri:level="1"><nlm:affiliation>University of British Columbia, Vancouver, Canada. vesna@physics.ubc.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author><author><name sortKey="De La Fuente Fernandez, Raul" sort="De La Fuente Fernandez, Raul" uniqKey="De La Fuente Fernandez R" first="Raúl" last="De La Fuente-Fernández">Raúl De La Fuente-Fernández</name></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name></author><author><name sortKey="Adams, John" sort="Adams, John" uniqKey="Adams J" first="John" last="Adams">John Adams</name></author><author><name sortKey="Stoessl, Jon" sort="Stoessl, Jon" uniqKey="Stoessl J" first="Jon" last="Stoessl">Jon Stoessl</name></author></analytic><series><title level="j">Brain : a journal of neurology</title><idno type="eISSN">1460-2156</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Age Factors</term><term>Age of Onset</term><term>Aged</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (blood)</term><term>Dihydroxyphenylalanine (analogs & derivatives)</term><term>Dopamine Agents (adverse effects)</term><term>Dopamine Agents (blood)</term><term>Dyskinesia, Drug-Induced (blood)</term><term>Dyskinesia, Drug-Induced (etiology)</term><term>Female</term><term>Humans</term><term>Levodopa (adverse effects)</term><term>Levodopa (blood)</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (blood)</term><term>Parkinson Disease (diagnostic imaging)</term><term>Parkinson Disease (drug therapy)</term><term>Tomography, Emission-Computed</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Dopamine Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Dihydroxyphenylalanine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antiparkinson Agents</term><term>Dopamine Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Age Factors</term><term>Age of Onset</term><term>Aged</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Tomography, Emission-Computed</term></keywords></textClass></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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16476675</PMID><DateCreated><Year>2006</Year><Month>03</Month><Day>17</Day></DateCreated><DateCompleted><Year>2006</Year><Month>04</Month><Day>17</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2156</ISSN><JournalIssue CitedMedium="Internet"><Volume>129</Volume><Issue>Pt 4</Issue><PubDate><Year>2006</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Brain : a journal of neurology</Title><ISOAbbreviation>Brain</ISOAbbreviation></Journal><ArticleTitle>Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications.</ArticleTitle><Pagination><MedlinePgn>1050-8</MedlinePgn></Pagination><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sossi</LastName><ForeName>Vesna</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>University of British Columbia, Vancouver, Canada. vesna@physics.ubc.ca</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de la Fuente-Fernández</LastName><ForeName>Raúl</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Schulzer</LastName><ForeName>Michael</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Adams</LastName><ForeName>John</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Stoessl</LastName><ForeName>Jon</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2006</Year><Month>02</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Brain</MedlineTA><NlmUniqueID>0372537</NlmUniqueID><ISSNLinking>0006-8950</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015259">Dopamine Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>2C598205QX</RegistryNumber><NameOfSubstance UI="C043437">fluorodopa F 18</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>63-84-3</RegistryNumber><NameOfSubstance 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UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014055" MajorTopicYN="N">Tomography, Emission-Computed</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>2</Month><Day>16</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2006</Year><Month>4</Month><Day>18</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>2</Month><Day>16</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">16476675</ArticleId><ArticleId IdType="pii">awl028</ArticleId><ArticleId IdType="doi">10.1093/brain/awl028</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Adams, John" sort="Adams, John" uniqKey="Adams J" first="John" last="Adams">John Adams</name><name sortKey="De La Fuente Fernandez, Raul" sort="De La Fuente Fernandez, Raul" uniqKey="De La Fuente Fernandez R" first="Raúl" last="De La Fuente-Fernández">Raúl De La Fuente-Fernández</name><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><name sortKey="Stoessl, Jon" sort="Stoessl, Jon" uniqKey="Stoessl J" first="Jon" last="Stoessl">Jon Stoessl</name></noCountry><country name="Canada"><noRegion><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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