Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson’s disease with mild cognitive impairment
Identifieur interne : 000717 ( Pmc/Corpus ); précédent : 000716; suivant : 000718Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson’s disease with mild cognitive impairment
Auteurs : Leigh Christopher ; Connie Marras ; Sarah Duff-Canning ; Yuko Koshimori ; Robert Chen ; Isabelle Boileau ; Barbara Segura ; Oury Monchi ; Anthony E. Lang ; Pablo Rusjan ; Sylvain Houle ; Antonio P. StrafellaSource :
- Brain : a journal of neurology [ 0006-8950 ] ; 2013.
Abstract
The ability to dynamically use various aspects of cognition is essential to daily function, and reliant on dopaminergic transmission in corticostriatal circuitry. Our aim was to investigate both striatal and cortical dopaminergic changes in patients with Parkinson’s disease with mild cognitive impairment, who represent a vulnerable group for the development of dementia. We hypothesized severe striatal dopamine denervation in the associative (i.e. cognitive) region and cortical D2 receptor abnormalities in the salience and executive networks in Parkinson’s disease with mild cognitive impairment compared with cognitively normal patients with Parkinson’s disease and healthy control subjects. We used positron emission tomography imaging with dopaminergic ligands 11C-dihydrotetrabenazine, to investigate striatal dopamine neuron integrity in the associative subdivision and 11C-FLB 457, to investigate cortical D2 receptor availability in patients with Parkinson’s disease (55–80 years of age) with mild cognitive impairment (
Url:
DOI: 10.1093/brain/awt337
PubMed: 24334314
PubMed Central: 4454524
Links to Exploration step
PMC:4454524Le document en format XML
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Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. 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Lang</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author><author><name sortKey="Rusjan, Pablo" sort="Rusjan, Pablo" uniqKey="Rusjan P" first="Pablo" last="Rusjan">Pablo Rusjan</name><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation></author><author><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation></author><author><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24334314</idno><idno type="pmc">4454524</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454524</idno><idno type="RBID">PMC:4454524</idno><idno type="doi">10.1093/brain/awt337</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000717</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000717</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson’s disease with mild cognitive impairment</title><author><name sortKey="Christopher, Leigh" sort="Christopher, Leigh" uniqKey="Christopher L" first="Leigh" last="Christopher">Leigh Christopher</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author><author><name sortKey="Duff Canning, Sarah" sort="Duff Canning, Sarah" uniqKey="Duff Canning S" first="Sarah" last="Duff-Canning">Sarah Duff-Canning</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Neuropsychology, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author><author><name sortKey="Koshimori, Yuko" sort="Koshimori, Yuko" uniqKey="Koshimori Y" first="Yuko" last="Koshimori">Yuko Koshimori</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author><author><name sortKey="Chen, Robert" sort="Chen, Robert" uniqKey="Chen R" first="Robert" last="Chen">Robert Chen</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author><author><name sortKey="Boileau, Isabelle" sort="Boileau, Isabelle" uniqKey="Boileau I" first="Isabelle" last="Boileau">Isabelle Boileau</name><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation></author><author><name sortKey="Segura, Barbara" sort="Segura, Barbara" uniqKey="Segura B" first="Barbara" last="Segura">Barbara Segura</name><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Catalonia, 08036, Spain</nlm:aff></affiliation></author><author><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><affiliation><nlm:aff id="A6">Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, Montréal, QC, H3W 1W4, Canada</nlm:aff></affiliation></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author><author><name sortKey="Rusjan, Pablo" sort="Rusjan, Pablo" uniqKey="Rusjan P" first="Pablo" last="Rusjan">Pablo Rusjan</name><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation></author><author><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation></author><author><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><affiliation><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, M5T 2S8, Canada</nlm:aff></affiliation></author></analytic><series><title level="j">Brain : a journal of neurology</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The ability to dynamically use various aspects of cognition is essential to daily function, and reliant on dopaminergic transmission in corticostriatal circuitry. Our aim was to investigate both striatal and cortical dopaminergic changes in patients with Parkinson’s disease with mild cognitive impairment, who represent a vulnerable group for the development of dementia. We hypothesized severe striatal dopamine denervation in the associative (i.e. cognitive) region and cortical D2 receptor abnormalities in the salience and executive networks in Parkinson’s disease with mild cognitive impairment compared with cognitively normal patients with Parkinson’s disease and healthy control subjects. We used positron emission tomography imaging with dopaminergic ligands <sup>11</sup>C-dihydrotetrabenazine, to investigate striatal dopamine neuron integrity in the associative subdivision and <sup>11</sup>C-FLB 457, to investigate cortical D2 receptor availability in patients with Parkinson’s disease (55–80 years of age) with mild cognitive impairment (<italic>n</italic> = 11), cognitively normal patients with Parkinson’s disease (<italic>n</italic> = 11) and age-matched healthy control subjects (<italic>n</italic> = 14). Subjects were administered a neuropsychological test battery to assess cognitive status and determine the relationship between dopaminergic changes and cognitive performance. We found that patients with mild cognitive impairment had severe striatal dopamine depletion in the associative (i.e. cognitive) subdivision as well as reduced D2 receptor availability in the bilateral insula, a key cognitive hub, compared to cognitively normal patients and healthy subjects after controlling for age, disease severity and daily dopaminergic medication intake. Associative striatal dopamine depletion was predictive of D2 receptor loss in the insula of patients with Parkinson’s disease with mild cognitive impairment, demonstrating interrelated striatal and cortical changes. Insular D2 levels also predicted executive abilities in these patients as measured using a composite executive <italic>z</italic>-score obtained from neuropsychological testing. Furthermore we assessed cortical thickness to ensure that D2 receptor changes were not confounded by brain atrophy. There was no difference between groups in cortical thickness in the insula, or any other cortical region of interest. These findings suggest that striatal dopamine denervation combined with insular D2 receptor loss underlie mild cognitive impairment in Parkinson’s disease and in particular decline in executive function. Furthermore, these findings suggest a crucial and direct role for dopaminergic modulation in the insula in facilitating cognitive function.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0372537</journal-id><journal-id journal-id-type="pubmed-jr-id">1917</journal-id><journal-id journal-id-type="nlm-ta">Brain</journal-id><journal-id journal-id-type="iso-abbrev">Brain</journal-id><journal-title-group><journal-title>Brain : a journal of neurology</journal-title></journal-title-group><issn pub-type="ppub">0006-8950</issn><issn pub-type="epub">1460-2156</issn></journal-meta><article-meta><article-id pub-id-type="pmid">24334314</article-id><article-id pub-id-type="pmc">4454524</article-id><article-id pub-id-type="doi">10.1093/brain/awt337</article-id><article-id pub-id-type="manuscript">CAMS4600</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson’s disease with mild cognitive impairment</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Christopher</surname><given-names>Leigh</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Marras</surname><given-names>Connie</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Duff-Canning</surname><given-names>Sarah</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Koshimori</surname><given-names>Yuko</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Boileau</surname><given-names>Isabelle</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Segura</surname><given-names>Barbara</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Monchi</surname><given-names>Oury</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Lang</surname><given-names>Anthony E.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Rusjan</surname><given-names>Pablo</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Houle</surname><given-names>Sylvain</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Strafella</surname><given-names>Antonio P.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib></contrib-group><aff id="A1"><label>1</label>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</aff><aff id="A2"><label>2</label>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, M5T 1R8, Canada</aff><aff id="A3"><label>3</label>Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, M5T 2S8, Canada</aff><aff id="A4"><label>4</label>Department of Neuropsychology, Toronto Western Hospital, UHN, University of Toronto, Ontario, M5T 2S8, Canada</aff><aff id="A5"><label>5</label>Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Catalonia, 08036, Spain</aff><aff id="A6"><label>6</label>Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, Montréal, QC, H3W 1W4, Canada</aff><author-notes><corresp id="FN1">Correspondence to: Antonio P. Strafella, M.D. PhD FRCPC, Toronto Western Hospital and Institute, CAMH-Research Imaging Centre, University of Toronto, Toronto, ON, Canada, M5T 1R8, <email>antonio.strafella@uhnres.utoronto.ca</email> or <email>antonio.strafella@camhpet.ca</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>28</day><month>5</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>12</day><month>12</month><year>2013</year></pub-date><pub-date pub-type="ppub"><month>2</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>03</day><month>6</month><year>2015</year></pub-date><volume>137</volume><issue>0 2</issue><fpage>565</fpage><lpage>575</lpage><pmc-comment>elocation-id from pubmed: 10.1093/brain/awt337</pmc-comment>
<permissions><copyright-statement>© The Author (2013). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.</copyright-statement><copyright-year>2013</copyright-year></permissions><abstract><p id="P1">The ability to dynamically use various aspects of cognition is essential to daily function, and reliant on dopaminergic transmission in corticostriatal circuitry. Our aim was to investigate both striatal and cortical dopaminergic changes in patients with Parkinson’s disease with mild cognitive impairment, who represent a vulnerable group for the development of dementia. We hypothesized severe striatal dopamine denervation in the associative (i.e. cognitive) region and cortical D2 receptor abnormalities in the salience and executive networks in Parkinson’s disease with mild cognitive impairment compared with cognitively normal patients with Parkinson’s disease and healthy control subjects. We used positron emission tomography imaging with dopaminergic ligands <sup>11</sup>C-dihydrotetrabenazine, to investigate striatal dopamine neuron integrity in the associative subdivision and <sup>11</sup>C-FLB 457, to investigate cortical D2 receptor availability in patients with Parkinson’s disease (55–80 years of age) with mild cognitive impairment (<italic>n</italic> = 11), cognitively normal patients with Parkinson’s disease (<italic>n</italic> = 11) and age-matched healthy control subjects (<italic>n</italic> = 14). Subjects were administered a neuropsychological test battery to assess cognitive status and determine the relationship between dopaminergic changes and cognitive performance. We found that patients with mild cognitive impairment had severe striatal dopamine depletion in the associative (i.e. cognitive) subdivision as well as reduced D2 receptor availability in the bilateral insula, a key cognitive hub, compared to cognitively normal patients and healthy subjects after controlling for age, disease severity and daily dopaminergic medication intake. Associative striatal dopamine depletion was predictive of D2 receptor loss in the insula of patients with Parkinson’s disease with mild cognitive impairment, demonstrating interrelated striatal and cortical changes. Insular D2 levels also predicted executive abilities in these patients as measured using a composite executive <italic>z</italic>-score obtained from neuropsychological testing. Furthermore we assessed cortical thickness to ensure that D2 receptor changes were not confounded by brain atrophy. There was no difference between groups in cortical thickness in the insula, or any other cortical region of interest. These findings suggest that striatal dopamine denervation combined with insular D2 receptor loss underlie mild cognitive impairment in Parkinson’s disease and in particular decline in executive function. Furthermore, these findings suggest a crucial and direct role for dopaminergic modulation in the insula in facilitating cognitive function.</p></abstract><kwd-group><kwd>Parkinson’s disease</kwd><kwd>mild cognitive impairment</kwd><kwd>positron emission tomography</kwd><kwd>dopamine</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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