A Tale of Two Factors: What Determines the Rate of Progression in Huntington's Disease? A Longitudinal MRI Study
Identifieur interne : 000732 ( PascalFrancis/Checkpoint ); précédent : 000731; suivant : 000733A Tale of Two Factors: What Determines the Rate of Progression in Huntington's Disease? A Longitudinal MRI Study
Auteurs : H. Diana Rosas [États-Unis] ; Martin Reuter [États-Unis] ; Gheorghe Doros [États-Unis] ; Stephanie Y. Lee [États-Unis] ; Tyler Triggs [États-Unis] ; Keith Malarick [États-Unis] ; Bruce Fischl [États-Unis] ; David H. Salat [États-Unis] ; Steven M. Hersch [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2011.
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Abstract
Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Hunting-ton's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease.
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Diana Rosas</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Reuter, Martin" sort="Reuter, Martin" uniqKey="Reuter M" first="Martin" last="Reuter">Martin Reuter</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA, and Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>MIT Computer Science and Al Lab, Division of Health Sciences and Technology</s1><s2>Cambridge, Masschusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cambridge, Masschusetts</wicri:noRegion></affiliation></author><author><name sortKey="Doros, Gheorghe" sort="Doros, Gheorghe" uniqKey="Doros G" first="Gheorghe" last="Doros">Gheorghe Doros</name><affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Department of Biostatistics, Boston University</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Lee, Stephanie Y" sort="Lee, Stephanie Y" uniqKey="Lee S" first="Stephanie Y." last="Lee">Stephanie Y. 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Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Triggs, Tyler" sort="Triggs, Tyler" uniqKey="Triggs T" first="Tyler" last="Triggs">Tyler Triggs</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Malarick, Keith" sort="Malarick, Keith" uniqKey="Malarick K" first="Keith" last="Malarick">Keith Malarick</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Fischl, Bruce" sort="Fischl, Bruce" uniqKey="Fischl B" first="Bruce" last="Fischl">Bruce Fischl</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA, and Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>MIT Computer Science and Al Lab, Division of Health Sciences and Technology</s1><s2>Cambridge, Masschusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cambridge, Masschusetts</wicri:noRegion></affiliation></author><author><name sortKey="Salat, David H" sort="Salat, David H" uniqKey="Salat D" first="David H." last="Salat">David H. Salat</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA, and Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hersch, Steven M" sort="Hersch, Steven M" uniqKey="Hersch S" first="Steven M." last="Hersch">Steven M. Hersch</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0380289</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 11-0380289 INIST</idno><idno type="RBID">Pascal:11-0380289</idno><idno type="wicri:Area/PascalFrancis/Corpus">000477</idno><idno type="wicri:Area/PascalFrancis/Curation">002841</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000732</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A Tale of Two Factors: What Determines the Rate of Progression in Huntington's Disease? A Longitudinal MRI Study</title><author><name sortKey="Rosas, H Diana" sort="Rosas, H Diana" uniqKey="Rosas H" first="H. Diana" last="Rosas">H. Diana Rosas</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Reuter, Martin" sort="Reuter, Martin" uniqKey="Reuter M" first="Martin" last="Reuter">Martin Reuter</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA, and Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>MIT Computer Science and Al Lab, Division of Health Sciences and Technology</s1><s2>Cambridge, Masschusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cambridge, Masschusetts</wicri:noRegion></affiliation></author><author><name sortKey="Doros, Gheorghe" sort="Doros, Gheorghe" uniqKey="Doros G" first="Gheorghe" last="Doros">Gheorghe Doros</name><affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Department of Biostatistics, Boston University</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Lee, Stephanie Y" sort="Lee, Stephanie Y" uniqKey="Lee S" first="Stephanie Y." last="Lee">Stephanie Y. Lee</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Triggs, Tyler" sort="Triggs, Tyler" uniqKey="Triggs T" first="Tyler" last="Triggs">Tyler Triggs</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Malarick, Keith" sort="Malarick, Keith" uniqKey="Malarick K" first="Keith" last="Malarick">Keith Malarick</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Fischl, Bruce" sort="Fischl, Bruce" uniqKey="Fischl B" first="Bruce" last="Fischl">Bruce Fischl</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA, and Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>MIT Computer Science and Al Lab, Division of Health Sciences and Technology</s1><s2>Cambridge, Masschusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cambridge, Masschusetts</wicri:noRegion></affiliation></author><author><name sortKey="Salat, David H" sort="Salat, David H" uniqKey="Salat D" first="David H." last="Salat">David H. Salat</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA, and Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hersch, Steven M" sort="Hersch, Steven M" uniqKey="Hersch S" first="Steven M." last="Hersch">Steven M. Hersch</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</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="2011">2011</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>Huntington disease</term><term>Nervous system diseases</term><term>Nuclear magnetic resonance imaging</term><term>Variability</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Chorée de Huntington</term><term>Atrophie</term><term>Pathologie du système nerveux</term><term>Imagerie RMN</term><term>Variabilité</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Hunting-ton's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>26</s2></fA05><fA06><s2>9</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>A Tale of Two Factors: What Determines the Rate of Progression in Huntington's Disease? A Longitudinal MRI Study</s1></fA08><fA11 i1="01" i2="1"><s1>ROSAS (H. Diana)</s1></fA11><fA11 i1="02" i2="1"><s1>REUTER (Martin)</s1></fA11><fA11 i1="03" i2="1"><s1>DOROS (Gheorghe)</s1></fA11><fA11 i1="04" i2="1"><s1>LEE (Stephanie Y.)</s1></fA11><fA11 i1="05" i2="1"><s1>TRIGGS (Tyler)</s1></fA11><fA11 i1="06" i2="1"><s1>MALARICK (Keith)</s1></fA11><fA11 i1="07" i2="1"><s1>FISCHL (Bruce)</s1></fA11><fA11 i1="08" i2="1"><s1>SALAT (David H.)</s1></fA11><fA11 i1="09" i2="1"><s1>HERSCH (Steven M.)</s1></fA11><fA14 i1="01"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="02"><s1>Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="03"><s1>MassGeneral Institute for Neurodegeneration, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="04"><s1>Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital</s1><s2>Charlestown, Massachusetts</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA, and Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="06"><s1>MIT Computer Science and Al Lab, Division of Health Sciences and Technology</s1><s2>Cambridge, Masschusetts</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Biostatistics, Boston University</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>3 aut.</sZ></fA14><fA20><s1>1691-1697</s1></fA20><fA21><s1>2011</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000508939410150</s5></fA43><fA44><s0>0000</s0><s1>© 2011 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>26 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>11-0380289</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Hunting-ton's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Chorée de Huntington</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Huntington disease</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Corea Huntington</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Atrophie</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Atrophy</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Atrofia</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Imagerie RMN</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Nuclear magnetic resonance imaging</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Imaginería RMN</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Variabilité</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Variability</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Variabilidad</s0><s5>10</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Maladie héréditaire</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Genetic disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Enfermedad hereditaria</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>41</s5></fC07><fN21><s1>262</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>États-Unis</li></country><region><li>Massachusetts</li></region></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Rosas, H Diana" sort="Rosas, H Diana" uniqKey="Rosas H" first="H. Diana" last="Rosas">H. Diana Rosas</name></region><name sortKey="Doros, Gheorghe" sort="Doros, Gheorghe" uniqKey="Doros G" first="Gheorghe" last="Doros">Gheorghe Doros</name><name sortKey="Fischl, Bruce" sort="Fischl, Bruce" uniqKey="Fischl B" first="Bruce" last="Fischl">Bruce Fischl</name><name sortKey="Fischl, Bruce" sort="Fischl, Bruce" uniqKey="Fischl B" first="Bruce" last="Fischl">Bruce Fischl</name><name sortKey="Fischl, Bruce" sort="Fischl, Bruce" uniqKey="Fischl B" first="Bruce" last="Fischl">Bruce Fischl</name><name sortKey="Hersch, Steven M" sort="Hersch, Steven M" uniqKey="Hersch S" first="Steven M." last="Hersch">Steven M. Hersch</name><name sortKey="Hersch, Steven M" sort="Hersch, Steven M" uniqKey="Hersch S" first="Steven M." last="Hersch">Steven M. Hersch</name><name sortKey="Lee, Stephanie Y" sort="Lee, Stephanie Y" uniqKey="Lee S" first="Stephanie Y." last="Lee">Stephanie Y. Lee</name><name sortKey="Lee, Stephanie Y" sort="Lee, Stephanie Y" uniqKey="Lee S" first="Stephanie Y." last="Lee">Stephanie Y. Lee</name><name sortKey="Lee, Stephanie Y" sort="Lee, Stephanie Y" uniqKey="Lee S" first="Stephanie Y." last="Lee">Stephanie Y. Lee</name><name sortKey="Lee, Stephanie Y" sort="Lee, Stephanie Y" uniqKey="Lee S" first="Stephanie Y." last="Lee">Stephanie Y. 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