ParkinsonCanadaV1, Main, Curation, bibRecord, 000C00

Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study

Identifieur interne : 000C00 ( Main/Curation ); précédent : 000B99; suivant : 000C01

Genetic 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'Brien [Royaume-Uni] ; David J. Brooks [Royaume-Uni, Danemark] ; David J. Burn [Royaume-Uni] ; Roger A. Barker [Royaume-Uni]

Source :

Brain [ 0006-8950 ] ; 2014.

RBID : Pascal:14-0238595

Descripteurs français

Pascal (Inist)
- Maladie de Parkinson, Pathologie du système nerveux, Cognition, Encéphale, Imagerie RMN.

English descriptors

KwdEn :
- Aged, Apolipoproteins E (genetics), Brain (physiopathology), Catechol O-Methyltransferase (genetics), Cognition, Cognition (physiology), Cognition Disorders (etiology), Cognition Disorders (psychology), Cohort Studies, Encephalon, Female, Humans, Image Processing, Computer-Assisted, Imagination (physiology), Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory (physiology), Middle Aged, Mitogen-Activated Protein Kinases (genetics), Nervous system diseases, Neuroimaging, Neuropsychological Tests, Nuclear magnetic resonance imaging, Parkinson Disease (genetics), Parkinson Disease (physiopathology), Parkinson disease, Psychomotor Performance (physiology), Rotation, Space Perception (physiology), tau Proteins (genetics).
MESH :
- chemical , genetics : Apolipoproteins E, Catechol O-Methyltransferase, Mitogen-Activated Protein Kinases, tau Proteins.
- etiology : Cognition Disorders.
- genetics : Parkinson Disease.
- physiology : Cognition, Imagination, Memory, Psychomotor Performance, Space Perception.
- physiopathology : Brain, Parkinson Disease.
- psychology : Cognition Disorders.
- Aged, Cohort Studies, Female, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Neuropsychological Tests, Rotation.

Abstract

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 (n = 168, median 8 months from diagnosis to participation) and matched control group (n = 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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163033

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<orgName type="university">Université de Cambridge</orgName>
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<author><name sortKey="Hampshire, Adam" sort="Hampshire, Adam" uniqKey="Hampshire A" first="Adam" last="Hampshire">Adam Hampshire</name>
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<author><name sortKey="Owen, Adrian M" sort="Owen, Adrian M" uniqKey="Owen A" first="Adrian M." last="Owen">Adrian M. Owen</name>
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</inist:fA14>
<country>Canada</country>
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<s3>CAN</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Canada</country>
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</placeName>
</affiliation>
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<author><name sortKey="Breen, David P" sort="Breen, David P" uniqKey="Breen D" first="David P." last="Breen">David P. Breen</name>
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</placeName>
<orgName type="university">Université de Cambridge</orgName>
</affiliation>
</author>
<author><name sortKey="Duncan, Gordon W" sort="Duncan, Gordon W" uniqKey="Duncan G" first="Gordon W." last="Duncan">Gordon W. Duncan</name>
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<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"><inist:fA14 i1="09"><s1>Griffith Health Institute and School of Medicine, Griffith University</s1>
<s2>Gold Coast</s2>
<s3>AUS</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Gold Coast</wicri:noRegion>
</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"><inist:fA14 i1="08"><s1>Institute for Ageing and Health, Newcastle University</s1>
<s2>Newcastle</s2>
<s3>GBR</s3>
<sZ>7 aut.</sZ>
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<country>Royaume-Uni</country>
<wicri:noRegion>Newcastle</wicri:noRegion>
</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"><inist:fA14 i1="08"><s1>Institute for Ageing and Health, Newcastle University</s1>
<s2>Newcastle</s2>
<s3>GBR</s3>
<sZ>7 aut.</sZ>
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</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"><inist:fA14 i1="10"><s1>Institute of Genetic Medicine, Newcastle University</s1>
<s2>Newcastle</s2>
<s3>GBR</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Newcastle</wicri:noRegion>
</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="4"><inist:fA14 i1="04"><s1>Behavioural and Clinical Neuroscience Institute, University of Cambridge</s1>
<s3>GBR</s3>
<sZ>2 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</affiliation>
</author>
<author><name sortKey="O Brien, John T" sort="O Brien, John T" uniqKey="O Brien J" first="John T." last="O'Brien">John T. O'Brien</name>
<affiliation wicri:level="4"><inist:fA14 i1="11"><s1>Department of Psychiatry, University of Cambridge</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
<sZ>13 aut.</sZ>
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<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</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="3"><inist:fA14 i1="12"><s1>Imperial College London</s1>
<s2>London</s2>
<s3>GBR</s3>
<sZ>14 aut.</sZ>
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<country>Royaume-Uni</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Clinical Medicine, Positron Emission Tomography Centre, Aarhus University</s1>
<s3>DNK</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Danemark</country>
<wicri:noRegion>Department of Clinical Medicine, Positron Emission Tomography Centre, Aarhus University</wicri:noRegion>
</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"><inist:fA14 i1="08"><s1>Institute for Ageing and Health, Newcastle University</s1>
<s2>Newcastle</s2>
<s3>GBR</s3>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
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<country>Royaume-Uni</country>
<wicri:noRegion>Newcastle</wicri:noRegion>
</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="4"><inist:fA14 i1="01"><s1>John van Geest Centre for Brain Repair, University of Cambridge</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
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<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</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>
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<seriesStmt><title level="j" type="main">Brain</title>
<title level="j" type="abbreviated">Brain</title>
<idno type="ISSN">0006-8950</idno>
</seriesStmt>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term>
<term>Apolipoproteins E (genetics)</term>
<term>Brain (physiopathology)</term>
<term>Catechol O-Methyltransferase (genetics)</term>
<term>Cognition</term>
<term>Cognition (physiology)</term>
<term>Cognition Disorders (etiology)</term>
<term>Cognition Disorders (psychology)</term>
<term>Cohort Studies</term>
<term>Encephalon</term>
<term>Female</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Imagination (physiology)</term>
<term>Longitudinal Studies</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Memory (physiology)</term>
<term>Middle Aged</term>
<term>Mitogen-Activated Protein Kinases (genetics)</term>
<term>Nervous system diseases</term>
<term>Neuroimaging</term>
<term>Neuropsychological Tests</term>
<term>Nuclear magnetic resonance imaging</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (physiopathology)</term>
<term>Parkinson disease</term>
<term>Psychomotor Performance (physiology)</term>
<term>Rotation</term>
<term>Space Perception (physiology)</term>
<term>tau Proteins (genetics)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Apolipoproteins E</term>
<term>Catechol O-Methyltransferase</term>
<term>Mitogen-Activated Protein Kinases</term>
<term>tau Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Cognition Disorders</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cognition</term>
<term>Imagination</term>
<term>Memory</term>
<term>Psychomotor Performance</term>
<term>Space Perception</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Brain</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Cognition Disorders</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Longitudinal Studies</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Neuroimaging</term>
<term>Neuropsychological Tests</term>
<term>Rotation</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term>
<term>Pathologie du   système nerveux</term>
<term>Cognition</term>
<term>Encéphale</term>
<term>Imagerie RMN</term>
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<front><div type="abstract" xml:lang="en">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 (n = 168, median 8 months from diagnosis to participation) and matched control group (n = 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.</div>
</front>
</TEI>
<double idat="0006-8950:2014:Nombela C:genetic:impact:on"><INIST><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study</title>
<author><name sortKey="Nombela, Cristina" sort="Nombela, Cristina" uniqKey="Nombela C" first="Cristina" last="Nombela">Cristina Nombela</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>John van Geest Centre for Brain Repair, University of Cambridge</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</affiliation>
</author>
<author><name sortKey="Rowe, James B" sort="Rowe, James B" uniqKey="Rowe J" first="James B." last="Rowe">James B. Rowe</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Clinical Neurosciences, University of Cambridge</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
<sZ>2 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Medical Research Council, Cognition and Brain Sciences Unit</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
<sZ>2 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Behavioural and Clinical Neuroscience Institute, University of Cambridge</s1>
<s3>GBR</s3>
<sZ>2 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</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="4"><inist:fA14 i1="01"><s1>John van Geest Centre for Brain Repair, University of Cambridge</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</affiliation>
</author>
<author><name sortKey="Hampshire, Adam" sort="Hampshire, Adam" uniqKey="Hampshire A" first="Adam" last="Hampshire">Adam Hampshire</name>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Computational, Cognitive and Clinical Neuroscience Laboratory, Imperial College London</s1>
<s2>London</s2>
<s3>GBR</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</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="3"><inist:fA14 i1="06"><s1>Brain and Mind Institute, University of Western Ontario</s1>
<s2>London</s2>
<s3>CAN</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Department of Psychology, University of Western Ontario</s1>
<s2>London</s2>
<s3>CAN</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</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="4"><inist:fA14 i1="01"><s1>John van Geest Centre for Brain Repair, University of Cambridge</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</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"><inist:fA14 i1="08"><s1>Institute for Ageing and Health, Newcastle University</s1>
<s2>Newcastle</s2>
<s3>GBR</s3>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Newcastle</wicri:noRegion>
</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"><inist:fA14 i1="09"><s1>Griffith Health Institute and School of Medicine, Griffith University</s1>
<s2>Gold Coast</s2>
<s3>AUS</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Gold Coast</wicri:noRegion>
</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"><inist:fA14 i1="08"><s1>Institute for Ageing and Health, Newcastle University</s1>
<s2>Newcastle</s2>
<s3>GBR</s3>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Newcastle</wicri:noRegion>
</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"><inist:fA14 i1="08"><s1>Institute for Ageing and Health, Newcastle University</s1>
<s2>Newcastle</s2>
<s3>GBR</s3>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Newcastle</wicri:noRegion>
</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"><inist:fA14 i1="10"><s1>Institute of Genetic Medicine, Newcastle University</s1>
<s2>Newcastle</s2>
<s3>GBR</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Newcastle</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Robbins, Trevor W" sort="Robbins, Trevor W" uniqKey="Robbins T" first="Trevor W." last="Robbins">Trevor W. Robbins</name>
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<author><name sortKey="Nombela, Cristina" sort="Nombela, Cristina" uniqKey="Nombela C" first="Cristina" last="Nombela">Cristina Nombela</name>
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</placeName>
<orgName type="university">Université de Cambridge</orgName>
</affiliation>
</author>
<author><name sortKey="Rowe, James B" sort="Rowe, James B" uniqKey="Rowe J" first="James B." last="Rowe">James B. Rowe</name>
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<orgName type="university">Université de Cambridge</orgName>
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</placeName>
<orgName type="university">Université de Cambridge</orgName>
</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>
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<orgName type="university">Université de Cambridge</orgName>
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<author><name sortKey="Hampshire, Adam" sort="Hampshire, Adam" uniqKey="Hampshire A" first="Adam" last="Hampshire">Adam Hampshire</name>
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<author><name sortKey="Owen, Adrian M" sort="Owen, Adrian M" uniqKey="Owen A" first="Adrian M." last="Owen">Adrian M. Owen</name>
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<author><name sortKey="Breen, David P" sort="Breen, David P" uniqKey="Breen D" first="David P." last="Breen">David P. Breen</name>
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<orgName type="university">Université de Cambridge</orgName>
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<author><name sortKey="Khoo, Tien K" sort="Khoo, Tien K" uniqKey="Khoo T" first="Tien K." last="Khoo">Tien K. Khoo</name>
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</inist:fA14>
<country>Australie</country>
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<author><name sortKey="Yarnall, Alison J" sort="Yarnall, Alison J" uniqKey="Yarnall A" first="Alison J." last="Yarnall">Alison J. Yarnall</name>
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<author><name sortKey="Chinnery, Patrick F" sort="Chinnery, Patrick F" uniqKey="Chinnery P" first="Patrick F." last="Chinnery">Patrick F. Chinnery</name>
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<author><name sortKey="O Brien, John T" sort="O Brien, John T" uniqKey="O Brien J" first="John T." last="O'Brien">John T. O'Brien</name>
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</placeName>
<orgName type="university">Université de Cambridge</orgName>
</affiliation>
</author>
<author><name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J." last="Brooks">David J. Brooks</name>
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<region type="région" nuts="1">Grand Londres</region>
</placeName>
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<sZ>14 aut.</sZ>
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<country>Danemark</country>
<wicri:noRegion>Department of Clinical Medicine, Positron Emission Tomography Centre, Aarhus University</wicri:noRegion>
</affiliation>
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<author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David J." last="Burn">David J. Burn</name>
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<s2>Newcastle</s2>
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<wicri:noRegion>Newcastle</wicri:noRegion>
</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="4"><inist:fA14 i1="01"><s1>John van Geest Centre for Brain Repair, University of Cambridge</s1>
<s2>Cambridge</s2>
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</placeName>
<orgName type="university">Université de Cambridge</orgName>
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</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>
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<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>Cognition</term>
<term>Encephalon</term>
<term>Nervous system diseases</term>
<term>Nuclear magnetic resonance imaging</term>
<term>Parkinson disease</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term>
<term>Pathologie du   système nerveux</term>
<term>Cognition</term>
<term>Encéphale</term>
<term>Imagerie RMN</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">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 (n = 168, median 8 months from diagnosis to participation) and matched control group (n = 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.</div>
</front>
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<PMC><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study</title>
<author><name sortKey="Nombela, Cristina" sort="Nombela, Cristina" uniqKey="Nombela C" first="Cristina" last="Nombela">Cristina Nombela</name>
<affiliation wicri:level="4"><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>
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<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rowe, James B" sort="Rowe, James B" uniqKey="Rowe J" first="James B." last="Rowe">James B. Rowe</name>
<affiliation wicri:level="4"><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>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</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>
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<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><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>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
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</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="4"><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>
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<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
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<author><name sortKey="Hampshire, Adam" sort="Hampshire, Adam" uniqKey="Hampshire A" first="Adam" last="Hampshire">Adam Hampshire</name>
<affiliation wicri:level="3"><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>
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<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
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<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>
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<author><name sortKey="Khoo, Tien K" sort="Khoo, Tien K" uniqKey="Khoo T" first="Tien K." last="Khoo">Tien K. Khoo</name>
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</author>
<author><name sortKey="Yarnall, Alison J" sort="Yarnall, Alison J" uniqKey="Yarnall A" first="Alison J." last="Yarnall">Alison J. Yarnall</name>
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<author><name sortKey="Robbins, Trevor W" sort="Robbins, Trevor W" uniqKey="Robbins T" first="Trevor W." last="Robbins">Trevor W. Robbins</name>
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<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>
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</placeName>
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<author><name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J." last="Brooks">David J. Brooks</name>
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</affiliation>
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<author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David J." last="Burn">David J. Burn</name>
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<author><name sortKey="Barker, Roger A" sort="Barker, Roger A" uniqKey="Barker R" first="Roger A." last="Barker">Roger A. Barker</name>
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<series><title level="j">Brain</title>
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<term>Apolipoproteins E (genetics)</term>
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<term>Catechol O-Methyltransferase (genetics)</term>
<term>Cognition (physiology)</term>
<term>Cognition Disorders (etiology)</term>
<term>Cognition Disorders (psychology)</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Imagination (physiology)</term>
<term>Longitudinal Studies</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Memory (physiology)</term>
<term>Middle Aged</term>
<term>Mitogen-Activated Protein Kinases (genetics)</term>
<term>Neuroimaging</term>
<term>Neuropsychological Tests</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (physiopathology)</term>
<term>Psychomotor Performance (physiology)</term>
<term>Rotation</term>
<term>Space Perception (physiology)</term>
<term>tau Proteins (genetics)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Apolipoproteins E</term>
<term>Catechol O-Methyltransferase</term>
<term>Mitogen-Activated Protein Kinases</term>
<term>tau Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Cognition Disorders</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cognition</term>
<term>Imagination</term>
<term>Memory</term>
<term>Psychomotor Performance</term>
<term>Space Perception</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Brain</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Cognition Disorders</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Cohort Studies</term>
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<term>Humans</term>
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<term>Longitudinal Studies</term>
<term>Magnetic Resonance Imaging</term>
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<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>
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   |wiki=    Wicri/Canada
   |area=    ParkinsonCanadaV1
   |flux=    Main
   |étape=   Curation
   |type=    RBID
   |clé=     Pascal:14-0238595
   |texte=   Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study
}}

This area was generated with Dilib version V0.6.29.
Data generation: Thu May 4 22:20:19 2017. Site generation: Fri Dec 23 23:17:26 2022

	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

La maladie de Parkinson au Canada (serveur d'exploration)

Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study

Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study

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