Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study
Identifieur interne : 000936 ( Pmc/Curation ); précédent : 000935; suivant : 000937Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study
Auteurs : Cristina Nombela [Royaume-Uni] ; James B. Rowe [Royaume-Uni] ; Sophie E. Winder-Rhodes [Royaume-Uni] ; Adam Hampshire [Royaume-Uni] ; Adrian M. Owen [Canada] ; David P. Breen [Royaume-Uni] ; Gordon W. Duncan [Royaume-Uni] ; Tien K. Khoo [Australie] ; Alison J. Yarnall [Royaume-Uni] ; Michael J. Firbank [Royaume-Uni] ; Patrick F. Chinnery [Royaume-Uni] ; Trevor W. Robbins [Royaume-Uni] ; John T. O Rien [Royaume-Uni] ; David J. Brooks [Royaume-Uni, Danemark] ; David J. Burn [Royaume-Uni] ; Roger A. Barker [Royaume-Uni]Source :
- Brain [ 0006-8950 ] ; 2014.
Abstract
See Dujardin (doi:
Url:
DOI: 10.1093/brain/awu201
PubMed: 25080285
PubMed Central: 4163033
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Rowe</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF2">2 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>2 Department of Clinical Neurosciences, University of Cambridge, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awu201-AFF3">3 Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>3 Medical Research Council, Cognition and Brain Sciences Unit, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awu201-AFF4">4 Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>4 Behavioural and Clinical Neuroscience Institute, University of Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Winder Rhodes, Sophie E" sort="Winder Rhodes, Sophie E" uniqKey="Winder Rhodes S" first="Sophie E." last="Winder-Rhodes">Sophie E. Winder-Rhodes</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF1">1 John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>1 John van Geest Centre for Brain Repair, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Hampshire, Adam" sort="Hampshire, Adam" uniqKey="Hampshire A" first="Adam" last="Hampshire">Adam Hampshire</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF5">5 Computational, Cognitive and Clinical Neuroscience Laboratory, Imperial College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>5 Computational, Cognitive and Clinical Neuroscience Laboratory, Imperial College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Owen, Adrian M" sort="Owen, Adrian M" uniqKey="Owen A" first="Adrian M." last="Owen">Adrian M. Owen</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF6">6 Brain and Mind Institute, University of Western Ontario, London, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>6 Brain and Mind Institute, University of Western Ontario, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awu201-AFF7">7 Department of Psychology, University of Western Ontario, London, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>7 Department of Psychology, University of Western Ontario, London</wicri:regionArea></affiliation></author><author><name sortKey="Breen, David P" sort="Breen, David P" uniqKey="Breen D" first="David P." last="Breen">David P. Breen</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF1">1 John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>1 John van Geest Centre for Brain Repair, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Duncan, Gordon W" sort="Duncan, Gordon W" uniqKey="Duncan G" first="Gordon W." last="Duncan">Gordon W. Duncan</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF8">8 Institute for Ageing and Health, Newcastle University, Newcastle, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>8 Institute for Ageing and Health, Newcastle University, Newcastle</wicri:regionArea></affiliation></author><author><name sortKey="Khoo, Tien K" sort="Khoo, Tien K" uniqKey="Khoo T" first="Tien K." last="Khoo">Tien K. Khoo</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF9">9 Griffith Health Institute and School of Medicine, Griffith University, Gold Coast, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>9 Griffith Health Institute and School of Medicine, Griffith University, Gold Coast</wicri:regionArea></affiliation></author><author><name sortKey="Yarnall, Alison J" sort="Yarnall, Alison J" uniqKey="Yarnall A" first="Alison J." last="Yarnall">Alison J. Yarnall</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF8">8 Institute for Ageing and Health, Newcastle University, Newcastle, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>8 Institute for Ageing and Health, Newcastle University, Newcastle</wicri:regionArea></affiliation></author><author><name sortKey="Firbank, Michael J" sort="Firbank, Michael J" uniqKey="Firbank M" first="Michael J." last="Firbank">Michael J. Firbank</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF8">8 Institute for Ageing and Health, Newcastle University, Newcastle, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>8 Institute for Ageing and Health, Newcastle University, Newcastle</wicri:regionArea></affiliation></author><author><name sortKey="Chinnery, Patrick F" sort="Chinnery, Patrick F" uniqKey="Chinnery P" first="Patrick F." last="Chinnery">Patrick F. Chinnery</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF10">10 Institute of Genetic Medicine, Newcastle University, Newcastle, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>10 Institute of Genetic Medicine, Newcastle University, Newcastle</wicri:regionArea></affiliation></author><author><name sortKey="Robbins, Trevor W" sort="Robbins, Trevor W" uniqKey="Robbins T" first="Trevor W." last="Robbins">Trevor W. Robbins</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF4">4 Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>4 Behavioural and Clinical Neuroscience Institute, University of Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="O Rien, John T" sort="O Rien, John T" uniqKey="O Rien J" first="John T." last="O Rien">John T. O Rien</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF11">11 Department of Psychiatry, University of Cambridge, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>11 Department of Psychiatry, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J." last="Brooks">David J. Brooks</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF12">12 Imperial College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>12 Imperial College London, London</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awu201-AFF13">13 Department of Clinical Medicine, Positron Emission Tomography Centre, Aarhus University, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>13 Department of Clinical Medicine, Positron Emission Tomography Centre, Aarhus University</wicri:regionArea></affiliation></author><author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David J." last="Burn">David J. Burn</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF8">8 Institute for Ageing and Health, Newcastle University, Newcastle, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>8 Institute for Ageing and Health, Newcastle University, Newcastle</wicri:regionArea></affiliation></author><author><name sortKey="Barker, Roger A" sort="Barker, Roger A" uniqKey="Barker R" first="Roger A." last="Barker">Roger A. Barker</name><affiliation wicri:level="1"><nlm:aff id="awu201-AFF1">1 John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>1 John van Geest Centre for Brain Repair, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author></analytic><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>See Dujardin (doi:<related-article id="d35e292" related-article-type="companion" ext-link-type="doi" xlink:href="10.1093/brain/awu218">10.1093/brain/awu218</related-article>) for a scientific commentary on this article. Nombela <italic>et al.</italic> present data from the ICICLE-PD study of cognition in newly diagnosed Parkinson’s disease. Consistent with the ‘Dual Syndrome’ hypothesis, impairments in executive function reflect a frontal dopaminergic syndrome modulated by COMT genotype, while visuospatial and memory deficits reflect disruption of temporo-parietal systems modulated by MAPT and APOE.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aarsland, D" uniqKey="Aarsland D">D Aarsland</name></author><author><name sortKey="Andersen, K" uniqKey="Andersen K">K Andersen</name></author><author><name sortKey="Larsen, Jp" uniqKey="Larsen J">JP Larsen</name></author><author><name sortKey="Lolk, A" uniqKey="Lolk A">A Lolk</name></author><author><name sortKey="Kragh Sorensen, P" uniqKey="Kragh Sorensen P">P Kragh-Sorensen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aarsland, D" uniqKey="Aarsland D">D Aarsland</name></author><author><name sortKey="Bronnick, K" uniqKey="Bronnick K">K Bronnick</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Brain</journal-id><journal-id journal-id-type="iso-abbrev">Brain</journal-id><journal-id journal-id-type="publisher-id">brainj</journal-id><journal-id journal-id-type="hwp">brain</journal-id><journal-title-group><journal-title>Brain</journal-title></journal-title-group><issn pub-type="ppub">0006-8950</issn><issn pub-type="epub">1460-2156</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25080285</article-id><article-id pub-id-type="pmc">4163033</article-id><article-id pub-id-type="doi">10.1093/brain/awu201</article-id><article-id pub-id-type="publisher-id">awu201</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Nombela</surname><given-names>Cristina</given-names></name><xref ref-type="aff" rid="awu201-AFF1"><sup>1</sup></xref><xref ref-type="author-notes" rid="awu201-FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Rowe</surname><given-names>James B.</given-names></name><xref ref-type="aff" rid="awu201-AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="awu201-AFF3"><sup>3</sup></xref><xref ref-type="aff" rid="awu201-AFF4"><sup>4</sup></xref><xref ref-type="author-notes" rid="awu201-FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Winder-Rhodes</surname><given-names>Sophie E.</given-names></name><xref ref-type="aff" rid="awu201-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hampshire</surname><given-names>Adam</given-names></name><xref ref-type="aff" rid="awu201-AFF5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Owen</surname><given-names>Adrian M.</given-names></name><xref ref-type="aff" rid="awu201-AFF6"><sup>6</sup></xref><xref ref-type="aff" rid="awu201-AFF7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Breen</surname><given-names>David P.</given-names></name><xref ref-type="aff" rid="awu201-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Duncan</surname><given-names>Gordon W.</given-names></name><xref ref-type="aff" rid="awu201-AFF8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Khoo</surname><given-names>Tien K.</given-names></name><xref ref-type="aff" rid="awu201-AFF9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yarnall</surname><given-names>Alison J.</given-names></name><xref ref-type="aff" rid="awu201-AFF8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Firbank</surname><given-names>Michael J.</given-names></name><xref ref-type="aff" rid="awu201-AFF8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chinnery</surname><given-names>Patrick F.</given-names></name><xref ref-type="aff" rid="awu201-AFF10"><sup>10</sup></xref></contrib><contrib contrib-type="author"><name><surname>Robbins</surname><given-names>Trevor W.</given-names></name><xref ref-type="aff" rid="awu201-AFF4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>O’Brien</surname><given-names>John T.</given-names></name><xref ref-type="aff" rid="awu201-AFF11"><sup>11</sup></xref></contrib><contrib contrib-type="author"><name><surname>Brooks</surname><given-names>David J.</given-names></name><xref ref-type="aff" rid="awu201-AFF12"><sup>12</sup></xref><xref ref-type="aff" rid="awu201-AFF13"><sup>13</sup></xref></contrib><contrib contrib-type="author"><name><surname>Burn</surname><given-names>David J.</given-names></name><xref ref-type="aff" rid="awu201-AFF8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><collab>the ICICLE-PD study group</collab></contrib><contrib contrib-type="author"><name><surname>Barker</surname><given-names>Roger A.</given-names></name><xref ref-type="aff" rid="awu201-AFF1"><sup>1</sup></xref></contrib><aff id="awu201-AFF1">1 John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK</aff><aff id="awu201-AFF2">2 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK</aff><aff id="awu201-AFF3">3 Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK</aff><aff id="awu201-AFF4">4 Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK</aff><aff id="awu201-AFF5">5 Computational, Cognitive and Clinical Neuroscience Laboratory, Imperial College London, London, UK</aff><aff id="awu201-AFF6">6 Brain and Mind Institute, University of Western Ontario, London, Canada</aff><aff id="awu201-AFF7">7 Department of Psychology, University of Western Ontario, London, Canada</aff><aff id="awu201-AFF8">8 Institute for Ageing and Health, Newcastle University, Newcastle, UK</aff><aff id="awu201-AFF9">9 Griffith Health Institute and School of Medicine, Griffith University, Gold Coast, Australia</aff><aff id="awu201-AFF10">10 Institute of Genetic Medicine, Newcastle University, Newcastle, UK</aff><aff id="awu201-AFF11">11 Department of Psychiatry, University of Cambridge, Cambridge, UK</aff><aff id="awu201-AFF12">12 Imperial College London, London, UK</aff><aff id="awu201-AFF13">13 Department of Clinical Medicine, Positron Emission Tomography Centre, Aarhus University, Denmark</aff></contrib-group><author-notes><corresp>Correspondence to: Cristina Nombela, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge Biomedical Campus, CB2 0PY, UK E-mail: <email>dra.cristinanombela@gmail.com</email></corresp><fn id="awu201-FN1"><p>*These authors contributed equally to this work.</p></fn><fn id="awu201-FN2"><p>See Dujardin (doi:<related-article id="d35e232" related-article-type="companion" ext-link-type="doi" xlink:href="10.1093/brain/awu218">10.1093/brain/awu218</related-article>) for a scientific commentary on this article.</p></fn></author-notes><pub-date pub-type="ppub"><month>10</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>30</day><month>7</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>30</day><month>7</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>137</volume><issue>10</issue><fpage>2743</fpage><lpage>2758</lpage><history><date date-type="received"><day>20</day><month>1</month><year>2014</year></date><date date-type="rev-recd"><day>11</day><month>5</month><year>2014</year></date><date date-type="accepted"><day>14</day><month>6</month><year>2014</year></date></history><permissions><copyright-statement>© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.</copyright-statement><copyright-year>2014</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/3.0/" license-type="creative-commons"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract abstract-type="precis"><p>See Dujardin (doi:<related-article id="d35e292" related-article-type="companion" ext-link-type="doi" xlink:href="10.1093/brain/awu218">10.1093/brain/awu218</related-article>) for a scientific commentary on this article. Nombela <italic>et al.</italic> present data from the ICICLE-PD study of cognition in newly diagnosed Parkinson’s disease. Consistent with the ‘Dual Syndrome’ hypothesis, impairments in executive function reflect a frontal dopaminergic syndrome modulated by COMT genotype, while visuospatial and memory deficits reflect disruption of temporo-parietal systems modulated by MAPT and APOE.</p></abstract><abstract><p>Parkinson’s disease is associated with multiple cognitive impairments and increased risk of dementia, but the extent of these deficits varies widely among patients. The ICICLE-PD study was established to define the characteristics and prevalence of cognitive change soon after diagnosis, in a representative cohort of patients, using a multimodal approach. Specifically, we tested the ‘Dual Syndrome’ hypothesis for cognitive impairment in Parkinson’s disease, which distinguishes an executive syndrome (affecting the frontostriatal regions due to dopaminergic deficits) from a posterior cortical syndrome (affecting visuospatial, mnemonic and semantic functions related to Lewy body pathology and secondary cholinergic loss). An incident Parkinson’s disease cohort (<italic>n</italic> = 168, median 8 months from diagnosis to participation) and matched control group (<italic>n</italic> = 85) were recruited to a neuroimaging study at two sites in the UK. All participants underwent clinical, neuropsychological and functional magnetic resonance imaging assessments. The three neuroimaging tasks (Tower of London, Spatial Rotations and Memory Encoding Tasks) were designed to probe executive, visuospatial and memory encoding domains, respectively. Patients were also genotyped for three polymorphisms associated with cognitive change in Parkinson’s disease and related disorders: (i) rs4680 for COMT Val158Met polymorphism; (ii) rs9468 for MAPT H1 versus H2 haplotype; and (iii) rs429358 for APOE-ε2, 3, 4. We identified performance deficits in all three cognitive domains, which were associated with regionally specific changes in cortical activation. Task-specific regional activations in Parkinson’s disease were linked with genetic variation: the rs4680 polymorphism modulated the effect of levodopa therapy on planning-related activations in the frontoparietal network; the MAPT haplotype modulated parietal activations associated with spatial rotations; and APOE allelic variation influenced the magnitude of activation associated with memory encoding. This study demonstrates that neurocognitive deficits are common even in recently diagnosed patients with Parkinson’s disease, and that the associated regional brain activations are influenced by genotype. These data further support the dual syndrome hypothesis of cognitive change in Parkinson’s disease. Longitudinal data will confirm the extent to which these early neurocognitive changes, and their genetic factors, influence the long-term risk of dementia in Parkinson’s disease. The combination of genetics and functional neuroimaging provides a potentially useful method for stratification and identification of candidate markers, in future clinical trials against cognitive decline in Parkinson’s disease.</p></abstract><kwd-group kwd-group-type="keywords"><kwd>Parkinson’s disease</kwd><kwd>cognition</kwd><kwd>functional MRI</kwd><kwd>genetics</kwd></kwd-group><counts><page-count count="16"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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