Rate and Acceleration of Whole-Brain Atrophy in Premanifest and Early Huntington's Disease
Identifieur interne : 002457 ( Main/Merge ); précédent : 002456; suivant : 002458Rate and Acceleration of Whole-Brain Atrophy in Premanifest and Early Huntington's Disease
Auteurs : Edward J. Wild [Royaume-Uni] ; Susie M. D. Henley [Royaume-Uni] ; Nicola Z. Hobbs [Royaume-Uni] ; Chris Frost [Royaume-Uni] ; David G. Macmanus [Royaume-Uni] ; Roger A. Barker [Royaume-Uni] ; Nick C. Fox [Royaume-Uni] ; Sarah J. Tabrizi [Royaume-Uni]Source :
- Movement disorders [ 0885-3185 ] ; 2010.
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Abstract
Huntington's disease (HD) produces progressive and ultimately widespread impairment ot bram function. Neostriatal atrophy alone cannot account for whole-brain losses seen postmortem, and the mutant huntingtin protein and its neuropathologic sequelae are evident throughout the brain. Whole-brain atrophy quantification encompasses the totality of mutant huntingtin's effects on brain volume and may be useful in tracking progression in trials. We studied whole-brain atrophy in HD using a 2-year follow-up design, with three annual MRI scans. We recruited 20 control subjects, 21 premanifest mutation carriers, and 40 patients with early HD and used the brain boundary shift integral to study rate and acceleration of atrophy. Among subjects with an acceptable quality 2-year scan pair, age- and gender-standardized mean brain atrophy rate was greater (P < 0.001) in the patients with HD (n = 21; 0.88%/yr; 95% confidence interval: 0.62-1.13%/yr) than that in controls (n = 13; 0.16%/yr; 0.00-0.32%/yr). In the 12 patients with early HD in whom acceleration could be directly assessed there was evidence (P = 0.048) of acceleration year-on-year (mean acceleration = 0.69% yr-2; 95% confidence interval: 0.01 % yr-2 to 1.37% yr-2), although this was not formally significantly different from that in controls (n = 7, P = 0.055). Statistically significantly increased atrophy rates and acceleration were not seen overall in the premanifest group, who were on average 18 years from predicted disease onset. We conclude that the study of whole-brain atrophy has the potential to inform our understanding of the neurobiology of HD and warrants further study as one means of assessing the outcomes of future clinical trials.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Rate and Acceleration of Whole-Brain Atrophy in Premanifest and Early Huntington's Disease</title><author><name sortKey="Wild, Edward J" sort="Wild, Edward J" uniqKey="Wild E" first="Edward J." last="Wild">Edward J. Wild</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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="Henley, Susie M D" sort="Henley, Susie M D" uniqKey="Henley S" first="Susie M. D." last="Henley">Susie M. D. Henley</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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="Hobbs, Nicola Z" sort="Hobbs, Nicola Z" uniqKey="Hobbs N" first="Nicola Z." last="Hobbs">Nicola Z. Hobbs</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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="Frost, Chris" sort="Frost, Chris" uniqKey="Frost C" first="Chris" last="Frost">Chris Frost</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Medical Statistics Unit, London School of Hygiene and Tropical Medicine</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="Macmanus, David G" sort="Macmanus, David G" uniqKey="Macmanus D" first="David G." last="Macmanus">David G. Macmanus</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>NMR Research Unit, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>5 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="Barker, Roger A" sort="Barker, Roger A" uniqKey="Barker R" first="Roger A." last="Barker">Roger A. Barker</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Clinical Neurosciences, Brain Repair Centre, Addenbrooke's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C." last="Fox">Nick C. Fox</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J." last="Tabrizi">Sarah J. Tabrizi</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0288336</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0288336 INIST</idno><idno type="RBID">Pascal:10-0288336</idno><idno type="wicri:Area/PascalFrancis/Corpus">000B18</idno><idno type="wicri:Area/PascalFrancis/Curation">002201</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000870</idno><idno type="wicri:doubleKey">0885-3185:2010:Wild E:rate:and:acceleration</idno><idno type="wicri:Area/Main/Merge">002457</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Rate and Acceleration of Whole-Brain Atrophy in Premanifest and Early Huntington's Disease</title><author><name sortKey="Wild, Edward J" sort="Wild, Edward J" uniqKey="Wild E" first="Edward J." last="Wild">Edward J. Wild</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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="Henley, Susie M D" sort="Henley, Susie M D" uniqKey="Henley S" first="Susie M. D." last="Henley">Susie M. D. Henley</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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="Hobbs, Nicola Z" sort="Hobbs, Nicola Z" uniqKey="Hobbs N" first="Nicola Z." last="Hobbs">Nicola Z. Hobbs</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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="Frost, Chris" sort="Frost, Chris" uniqKey="Frost C" first="Chris" last="Frost">Chris Frost</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Medical Statistics Unit, London School of Hygiene and Tropical Medicine</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="Macmanus, David G" sort="Macmanus, David G" uniqKey="Macmanus D" first="David G." last="Macmanus">David G. Macmanus</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>NMR Research Unit, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>5 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="Barker, Roger A" sort="Barker, Roger A" uniqKey="Barker R" first="Roger A." last="Barker">Roger A. Barker</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Clinical Neurosciences, Brain Repair Centre, Addenbrooke's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C." last="Fox">Nick C. Fox</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Dementia Research Centre, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 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><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J." last="Tabrizi">Sarah J. Tabrizi</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurodegenerative Disease, UCL Institute of Neurology</s1><s2>London</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 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></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Atrophy</term><term>Encephalon</term><term>Huntington disease</term><term>Nervous system diseases</term><term>Nuclear magnetic resonance imaging</term><term>Volumetric analysis</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Atrophie</term><term>Chorée de Huntington</term><term>Pathologie du système nerveux</term><term>Encéphale</term><term>Volumétrie</term><term>Imagerie RMN</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Huntington's disease (HD) produces progressive and ultimately widespread impairment ot bram function. Neostriatal atrophy alone cannot account for whole-brain losses seen postmortem, and the mutant huntingtin protein and its neuropathologic sequelae are evident throughout the brain. Whole-brain atrophy quantification encompasses the totality of mutant huntingtin's effects on brain volume and may be useful in tracking progression in trials. We studied whole-brain atrophy in HD using a 2-year follow-up design, with three annual MRI scans. We recruited 20 control subjects, 21 premanifest mutation carriers, and 40 patients with early HD and used the brain boundary shift integral to study rate and acceleration of atrophy. Among subjects with an acceptable quality 2-year scan pair, age- and gender-standardized mean brain atrophy rate was greater (P < 0.001) in the patients with HD (n = 21; 0.88%/yr; 95% confidence interval: 0.62-1.13%/yr) than that in controls (n = 13; 0.16%/yr; 0.00-0.32%/yr). In the 12 patients with early HD in whom acceleration could be directly assessed there was evidence (P = 0.048) of acceleration year-on-year (mean acceleration = 0.69% yr<sup>-2</sup>; 95% confidence interval: 0.01 % yr<sup>-2</sup> to 1.37% yr<sup>-2</sup>), although this was not formally significantly different from that in controls (n = 7, P = 0.055). Statistically significantly increased atrophy rates and acceleration were not seen overall in the premanifest group, who were on average 18 years from predicted disease onset. We conclude that the study of whole-brain atrophy has the potential to inform our understanding of the neurobiology of HD and warrants further study as one means of assessing the outcomes of future clinical trials.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Wild, Edward J" sort="Wild, Edward J" uniqKey="Wild E" first="Edward J." last="Wild">Edward J. Wild</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="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C." last="Fox">Nick C. Fox</name><name sortKey="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C." last="Fox">Nick C. Fox</name><name sortKey="Frost, Chris" sort="Frost, Chris" uniqKey="Frost C" first="Chris" last="Frost">Chris Frost</name><name sortKey="Frost, Chris" sort="Frost, Chris" uniqKey="Frost C" first="Chris" last="Frost">Chris Frost</name><name sortKey="Henley, Susie M D" sort="Henley, Susie M D" uniqKey="Henley S" first="Susie M. D." last="Henley">Susie M. D. Henley</name><name sortKey="Henley, Susie M D" sort="Henley, Susie M D" uniqKey="Henley S" first="Susie M. D." last="Henley">Susie M. D. Henley</name><name sortKey="Hobbs, Nicola Z" sort="Hobbs, Nicola Z" uniqKey="Hobbs N" first="Nicola Z." last="Hobbs">Nicola Z. Hobbs</name><name sortKey="Hobbs, Nicola Z" sort="Hobbs, Nicola Z" uniqKey="Hobbs N" first="Nicola Z." last="Hobbs">Nicola Z. Hobbs</name><name sortKey="Macmanus, David G" sort="Macmanus, David G" uniqKey="Macmanus D" first="David G." last="Macmanus">David G. Macmanus</name><name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J." last="Tabrizi">Sarah J. Tabrizi</name><name sortKey="Wild, Edward J" sort="Wild, Edward J" uniqKey="Wild E" first="Edward J." last="Wild">Edward J. Wild</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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