Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications
Identifieur interne : 001365 ( Main/Exploration ); précédent : 001364; suivant : 001366Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications
Auteurs : Vesna Sossi ; Rau L De La Fuente-Ferna Ndez [Espagne] ; Michael Schulzer ; John Adams [Canada] ; Jon StoesslSource :
- Brain [ 0006-8950 ] ; 2006-04.
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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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type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:002F98A4082AAD5FAFCC17DD395396D834365C29</idno><date when="2006" year="2006">2006</date><idno type="doi">10.1093/brain/awl028</idno><idno type="url">https://api.istex.fr/document/002F98A4082AAD5FAFCC17DD395396D834365C29/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001044</idno><idno type="wicri:Area/Main/Curation">000E54</idno><idno type="wicri:Area/Main/Exploration">001365</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" 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:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="De La Fuente Ferna Ndez, Rau L" sort="De La 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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><affiliations><list><country><li>Canada</li><li>Espagne</li></country><region><li>Galice</li></region></list><tree><noCountry><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><name sortKey="Stoessl, Jon" sort="Stoessl, Jon" uniqKey="Stoessl J" first="Jon" last="Stoessl">Jon Stoessl</name></noCountry><country name="Espagne"><region name="Galice"><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></region></country><country name="Canada"><noRegion><name sortKey="Adams, John" sort="Adams, John" uniqKey="Adams J" first="John" last="Adams">John Adams</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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