Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study
Identifieur interne : 000C00 ( Main/Exploration ); précédent : 000B99; suivant : 000C01Genetic 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.
Descripteurs français
- Pascal (Inist)
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:
Affiliations:
- Australie, Canada, Danemark, Royaume-Uni
- Angleterre, Angleterre de l'Est, Grand Londres
- Cambridge, Londres
- Université de Cambridge
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Le document en format XML
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<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>
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</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>
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<country>Royaume-Uni</country>
<wicri:noRegion>Newcastle</wicri:noRegion>
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</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>
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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="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>
</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="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>
<sZ>15 aut.</sZ>
</inist:fA14>
<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>
<sZ>16 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>
</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>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>
</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>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Canada</li>
<li>Danemark</li>
<li>Royaume-Uni</li>
</country>
<region><li>Angleterre</li>
<li>Angleterre de l'Est</li>
<li>Grand Londres</li>
</region>
<settlement><li>Cambridge</li>
<li>Londres</li>
</settlement>
<orgName><li>Université de Cambridge</li>
</orgName>
</list>
<tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Nombela, Cristina" sort="Nombela, Cristina" uniqKey="Nombela C" first="Cristina" last="Nombela">Cristina Nombela</name>
</region>
<name sortKey="Barker, Roger A" sort="Barker, Roger A" uniqKey="Barker R" first="Roger A." last="Barker">Roger A. Barker</name>
<name sortKey="Breen, David P" sort="Breen, David P" uniqKey="Breen D" first="David P." last="Breen">David P. Breen</name>
<name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J." last="Brooks">David J. Brooks</name>
<name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David J." last="Burn">David J. Burn</name>
<name sortKey="Chinnery, Patrick F" sort="Chinnery, Patrick F" uniqKey="Chinnery P" first="Patrick F." last="Chinnery">Patrick F. Chinnery</name>
<name sortKey="Duncan, Gordon W" sort="Duncan, Gordon W" uniqKey="Duncan G" first="Gordon W." last="Duncan">Gordon W. Duncan</name>
<name sortKey="Firbank, Michael J" sort="Firbank, Michael J" uniqKey="Firbank M" first="Michael J." last="Firbank">Michael J. Firbank</name>
<name sortKey="Hampshire, Adam" sort="Hampshire, Adam" uniqKey="Hampshire A" first="Adam" last="Hampshire">Adam Hampshire</name>
<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>
<name sortKey="Robbins, Trevor W" sort="Robbins, Trevor W" uniqKey="Robbins T" first="Trevor W." last="Robbins">Trevor W. Robbins</name>
<name sortKey="Rowe, James B" sort="Rowe, James B" uniqKey="Rowe J" first="James B." last="Rowe">James B. Rowe</name>
<name sortKey="Rowe, James B" sort="Rowe, James B" uniqKey="Rowe J" first="James B." last="Rowe">James B. Rowe</name>
<name sortKey="Rowe, James B" sort="Rowe, James B" uniqKey="Rowe J" first="James B." last="Rowe">James B. Rowe</name>
<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>
<name sortKey="Yarnall, Alison J" sort="Yarnall, Alison J" uniqKey="Yarnall A" first="Alison J." last="Yarnall">Alison J. Yarnall</name>
</country>
<country name="Canada"><region name="Angleterre"><name sortKey="Owen, Adrian M" sort="Owen, Adrian M" uniqKey="Owen A" first="Adrian M." last="Owen">Adrian M. Owen</name>
</region>
<name sortKey="Owen, Adrian M" sort="Owen, Adrian M" uniqKey="Owen A" first="Adrian M." last="Owen">Adrian M. Owen</name>
</country>
<country name="Australie"><noRegion><name sortKey="Khoo, Tien K" sort="Khoo, Tien K" uniqKey="Khoo T" first="Tien K." last="Khoo">Tien K. Khoo</name>
</noRegion>
</country>
<country name="Danemark"><noRegion><name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J." last="Brooks">David J. Brooks</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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