Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease
Identifieur interne : 000401 ( Main/Exploration ); précédent : 000400; suivant : 000402Age‐specific progression of nigrostriatal dysfunction in Parkinson's disease
Auteurs : Raúl De La Fuente-Fernández [Canada] ; Michael Schulzer [Canada] ; Lisa Kuramoto [Canada] ; Jacquelyn Cragg [Canada] ; Nandhagopal Ramachandiran [Canada] ; Wing L. Au [Canada] ; Edwin Mak [Canada] ; Jess Mckenzie [Canada] ; Siobhan Mccormick [Canada] ; Vesna Sossi [Canada] ; Thomas J. Ruth [Canada] ; Chong S. Lee [Canada] ; Donald B. Calne [Canada] ; A. Jon Stoessl [Canada]Source :
- Annals of Neurology [ 0364-5134 ] ; 2011-05.
Abstract
Objective:: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods:: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d‐threo‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐[18F]‐fluoro‐L‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase. Results:: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p < 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation:: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011;
Url:
DOI: 10.1002/ana.22284
Affiliations:
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Au</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Mak, Edwin" sort="Mak, Edwin" uniqKey="Mak E" first="Edwin" last="Mak">Edwin Mak</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Mckenzie, Jess" sort="Mckenzie, Jess" uniqKey="Mckenzie J" first="Jess" last="Mckenzie">Jess Mckenzie</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Mccormick, Siobhan" sort="Mccormick, Siobhan" uniqKey="Mccormick S" first="Siobhan" last="Mccormick">Siobhan Mccormick</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>TRIUMF, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></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 wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Calne, Donald B" sort="Calne, Donald B" uniqKey="Calne D" first="Donald B." last="Calne">Donald B. 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Jon Stoessl</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-05">2011-05</date><biblScope unit="volume">69</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="803">803</biblScope><biblScope unit="page" to="810">810</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">E02D1CF0A2675938DABC1F708869227D8EA17ED8</idno><idno type="DOI">10.1002/ana.22284</idno><idno type="ArticleID">ANA22284</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective:: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods:: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d‐threo‐methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6‐[18F]‐fluoro‐L‐dopa, to estimate the activity of the enzyme dopa‐decarboxylase. Results:: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p < 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation:: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011;</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="De La Fuente Ernandez, Raul" sort="De La Fuente Ernandez, Raul" uniqKey="De La Fuente Ernandez R" first="Raúl" last="De La Fuente-Fernández">Raúl De La Fuente-Fernández</name></noRegion><name sortKey="Au, Wing L" sort="Au, Wing L" uniqKey="Au W" first="Wing L." last="Au">Wing L. Au</name><name sortKey="Calne, Donald B" sort="Calne, Donald B" uniqKey="Calne D" first="Donald B." last="Calne">Donald B. Calne</name><name sortKey="Cragg, Jacquelyn" sort="Cragg, Jacquelyn" uniqKey="Cragg J" first="Jacquelyn" last="Cragg">Jacquelyn Cragg</name><name sortKey="Kuramoto, Lisa" sort="Kuramoto, Lisa" uniqKey="Kuramoto L" first="Lisa" last="Kuramoto">Lisa Kuramoto</name><name sortKey="Lee, Chong S" sort="Lee, Chong S" uniqKey="Lee C" first="Chong S." last="Lee">Chong S. Lee</name><name sortKey="Mak, Edwin" sort="Mak, Edwin" uniqKey="Mak E" first="Edwin" last="Mak">Edwin Mak</name><name sortKey="Mccormick, Siobhan" sort="Mccormick, Siobhan" uniqKey="Mccormick S" first="Siobhan" last="Mccormick">Siobhan Mccormick</name><name sortKey="Mckenzie, Jess" sort="Mckenzie, Jess" uniqKey="Mckenzie J" first="Jess" last="Mckenzie">Jess Mckenzie</name><name sortKey="Ramachandiran, Nandhagopal" sort="Ramachandiran, Nandhagopal" uniqKey="Ramachandiran N" first="Nandhagopal" last="Ramachandiran">Nandhagopal Ramachandiran</name><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><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, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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