Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson's disease with mild cognitive impairment
Identifieur interne : 000B77 ( PascalFrancis/Curation ); précédent : 000B76; suivant : 000B78Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson's disease with mild cognitive impairment
Auteurs : Leigh Christopher [Canada] ; Connie Marras [Canada] ; Sarah Duff-Canning [Canada] ; Yuko Koshimori [Canada] ; Robert Chen [Canada] ; Isabelle Boileau [Canada] ; Barbara Segura [Canada, Espagne] ; Oury Monchi [Canada] ; Anthony E. Lang [Canada] ; Pablo Rusjan [Canada] ; Sylvain Houle [Canada] ; Antonio P. Strafella [Canada]Source :
- Brain [ 0006-8950 ] ; 2014.
Descripteurs français
- Pascal (Inist)
English descriptors
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Abstract
The ability to dynamically use various aspects of cognition is essential to daily function, and reliant on dopaminergic transmission in cortico-striatal 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 (n = 11), cognitively normal patients with Parkinson's disease (n = 11) and age-matched healthy control subjects (n = 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 z-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.
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Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Boileau, Isabelle" sort="Boileau, Isabelle" uniqKey="Boileau I" first="Isabelle" last="Boileau">Isabelle Boileau</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Segura, Barbara" sort="Segura, Barbara" uniqKey="Segura B" first="Barbara" last="Segura">Barbara Segura</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Brain, Imaging and Behaviour - Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Psychiatry and Clinical Psychobiology, University of Barcelona</s1><s2>Barcelona, Catalonia, 08036</s2><s3>ESP</s3><sZ>7 aut.</sZ></inist:fA14><country>Espagne</country></affiliation></author><author><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal</s1><s2>Montréal, QC, H3W 1W4</s2><s3>CAN</s3><sZ>8 aut.</sZ></inist:fA14><country>Canada</country></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 wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. 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Strafella</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Brain, Imaging and Behaviour - Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0052747</idno><date when="2014">2014</date><idno type="stanalyst">PASCAL 14-0052747 INIST</idno><idno type="RBID">Pascal:14-0052747</idno><idno type="wicri:Area/PascalFrancis/Corpus">000041</idno><idno type="stanalyst">FRANCIS 14-0052747 INIST</idno><idno type="wicri:Area/PascalFrancis/Corpus">000057</idno><idno type="wicri:Area/PascalFrancis/Curation">000B77</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">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 wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Brain, Imaging and Behaviour - Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></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 wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Neuropsychology, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Koshimori, Yuko" sort="Koshimori, Yuko" uniqKey="Koshimori Y" first="Yuko" last="Koshimori">Yuko Koshimori</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Brain, Imaging and Behaviour - Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Chen, Robert" sort="Chen, Robert" uniqKey="Chen R" first="Robert" last="Chen">Robert Chen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Boileau, Isabelle" sort="Boileau, Isabelle" uniqKey="Boileau I" first="Isabelle" last="Boileau">Isabelle Boileau</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Segura, Barbara" sort="Segura, Barbara" uniqKey="Segura B" first="Barbara" last="Segura">Barbara Segura</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Brain, Imaging and Behaviour - Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Psychiatry and Clinical Psychobiology, University of Barcelona</s1><s2>Barcelona, Catalonia, 08036</s2><s3>ESP</s3><sZ>7 aut.</sZ></inist:fA14><country>Espagne</country></affiliation></author><author><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal</s1><s2>Montréal, QC, H3W 1W4</s2><s3>CAN</s3><sZ>8 aut.</sZ></inist:fA14><country>Canada</country></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 wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Rusjan, Pablo" sort="Rusjan, Pablo" uniqKey="Rusjan P" first="Pablo" last="Rusjan">Pablo Rusjan</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></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 wicri:level="1"><inist:fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Brain, Imaging and Behaviour - Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author></analytic><series><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cognitive disorder</term><term>Dopamine</term><term>Emission tomography</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Positron emission tomography</term><term>mild cognitive impairment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Trouble cognitif</term><term>Maladie de Parkinson</term><term>Déficit cognitif léger</term><term>Pathologie du système nerveux</term><term>Dopamine</term><term>Tomoscintigraphie</term><term>Tomographie par émission de positons</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The ability to dynamically use various aspects of cognition is essential to daily function, and reliant on dopaminergic transmission in cortico-striatal 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 (n = 11), cognitively normal patients with Parkinson's disease (n = 11) and age-matched healthy control subjects (n = 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 z-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.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0006-8950</s0></fA01><fA03 i2="1"><s0>Brain</s0></fA03><fA05><s2>137</s2></fA05><fA06><s3>p. 2</s3></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson's disease with mild cognitive impairment</s1></fA08><fA11 i1="01" i2="1"><s1>CHRISTOPHER (Leigh)</s1></fA11><fA11 i1="02" i2="1"><s1>MARRAS (Connie)</s1></fA11><fA11 i1="03" i2="1"><s1>DUFF-CANNING (Sarah)</s1></fA11><fA11 i1="04" i2="1"><s1>KOSHIMORI (Yuko)</s1></fA11><fA11 i1="05" i2="1"><s1>CHEN (Robert)</s1></fA11><fA11 i1="06" i2="1"><s1>BOILEAU (Isabelle)</s1></fA11><fA11 i1="07" i2="1"><s1>SEGURA (Barbara)</s1></fA11><fA11 i1="08" i2="1"><s1>MONCHI (Oury)</s1></fA11><fA11 i1="09" i2="1"><s1>LANG (Anthony E.)</s1></fA11><fA11 i1="10" i2="1"><s1>RUSJAN (Pablo)</s1></fA11><fA11 i1="11" i2="1"><s1>HOULE (Sylvain)</s1></fA11><fA11 i1="12" i2="1"><s1>STRAFELLA (Antonio P.)</s1></fA11><fA14 i1="01"><s1>Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="02"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Toronto, Ontario, M5T 1R8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="03"><s1>Division of Brain, Imaging and Behaviour - Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Neuropsychology, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario, M5T 2S8</s2><s3>CAN</s3><sZ>3 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Psychiatry and Clinical Psychobiology, University of Barcelona</s1><s2>Barcelona, Catalonia, 08036</s2><s3>ESP</s3><sZ>7 aut.</sZ></fA14><fA14 i1="06"><s1>Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal</s1><s2>Montréal, QC, H3W 1W4</s2><s3>CAN</s3><sZ>8 aut.</sZ></fA14><fA20><s1>565-575</s1></fA20><fA21><s1>2014</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>998</s2><s5>354000505712160210</s5></fA43><fA44><s0>0000</s0><s1>© 2014 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>1 p.1/4</s0></fA45><fA47 i1="01" i2="1"><s0>14-0052747</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Brain</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>The ability to dynamically use various aspects of cognition is essential to daily function, and reliant on dopaminergic transmission in cortico-striatal 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 (n = 11), cognitively normal patients with Parkinson's disease (n = 11) and age-matched healthy control subjects (n = 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 z-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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17G</s0></fC02><fC02 i1="02" i2="X"><s0>002B18E</s0></fC02><fC02 i1="03" i2="X"><s0>002B17A01</s0></fC02><fC02 i1="04" i2="X"><s0>002B17A03</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Trouble cognitif</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Cognitive disorder</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Trastorno cognitivo</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Déficit cognitif léger</s0><s2>NM</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>mild cognitive impairment</s0><s2>NM</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Disturbio cognitivo ligero</s0><s2>NM</s2><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Dopamine</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Dopamine</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Dopamina</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Tomoscintigraphie</s0><s5>10</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Emission tomography</s0><s5>10</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Tomocentelleografía</s0><s5>10</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Tomographie par émission de positons</s0><s5>11</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Positron emission tomography</s0><s5>11</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Tomografía emisión positrones</s0><s5>11</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Catécholamine</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Catecholamine</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Catecolamina</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Neurotransmetteur</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Neurotransmitter</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Neurotransmisor</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>41</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>42</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>42</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>42</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Exploration radioisotopique</s0><s5>44</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Radionuclide study</s0><s5>44</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Exploración radioisotópica</s0><s5>44</s5></fC07><fN21><s1>062</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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