Tracking motor impairments in the progression of Huntington's disease.
Identifieur interne : 000707 ( PubMed/Corpus ); précédent : 000706; suivant : 000708Tracking motor impairments in the progression of Huntington's disease.
Auteurs : Jeffery D. Long ; Jane S. Paulsen ; Karen Marder ; Ying Zhang ; Ji-In Kim ; James A. MillsSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- MESH :
- diagnosis : Huntington Disease, Motor Neuron Disease.
- genetics : Huntington Disease, Motor Neuron Disease.
- methods : Genetic Testing.
- Adult, Aged, Disease Progression, Genetic Predisposition to Disease, Humans, Linear Models, Middle Aged, Neuropsychological Tests.
Abstract
The Unified Huntington's Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene-expanded participants from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntington's disease research and the planning of clinical trials of efficacy are discussed.
DOI: 10.1002/mds.25657
PubMed: 24150908
Links to Exploration step
pubmed:24150908Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Tracking motor impairments in the progression of Huntington's disease.</title><author><name sortKey="Long, Jeffery D" sort="Long, Jeffery D" uniqKey="Long J" first="Jeffery D" last="Long">Jeffery D. Long</name><affiliation><nlm:affiliation>Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Paulsen, Jane S" sort="Paulsen, Jane S" uniqKey="Paulsen J" first="Jane S" last="Paulsen">Jane S. Paulsen</name></author><author><name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name></author><author><name sortKey="Zhang, Ying" sort="Zhang, Ying" uniqKey="Zhang Y" first="Ying" last="Zhang">Ying Zhang</name></author><author><name sortKey="Kim, Ji In" sort="Kim, Ji In" uniqKey="Kim J" first="Ji-In" last="Kim">Ji-In Kim</name></author><author><name sortKey="Mills, James A" sort="Mills, James A" uniqKey="Mills J" first="James A" last="Mills">James A. Mills</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24150908</idno><idno type="pmid">24150908</idno><idno type="doi">10.1002/mds.25657</idno><idno type="wicri:Area/PubMed/Corpus">000707</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Tracking motor impairments in the progression of Huntington's disease.</title><author><name sortKey="Long, Jeffery D" sort="Long, Jeffery D" uniqKey="Long J" first="Jeffery D" last="Long">Jeffery D. Long</name><affiliation><nlm:affiliation>Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Paulsen, Jane S" sort="Paulsen, Jane S" uniqKey="Paulsen J" first="Jane S" last="Paulsen">Jane S. Paulsen</name></author><author><name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name></author><author><name sortKey="Zhang, Ying" sort="Zhang, Ying" uniqKey="Zhang Y" first="Ying" last="Zhang">Ying Zhang</name></author><author><name sortKey="Kim, Ji In" sort="Kim, Ji In" uniqKey="Kim J" first="Ji-In" last="Kim">Ji-In Kim</name></author><author><name sortKey="Mills, James A" sort="Mills, James A" uniqKey="Mills J" first="James A" last="Mills">James A. Mills</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Disease Progression</term><term>Genetic Predisposition to Disease</term><term>Genetic Testing (methods)</term><term>Humans</term><term>Huntington Disease (diagnosis)</term><term>Huntington Disease (genetics)</term><term>Linear Models</term><term>Middle Aged</term><term>Motor Neuron Disease (diagnosis)</term><term>Motor Neuron Disease (genetics)</term><term>Neuropsychological Tests</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Huntington Disease</term><term>Motor Neuron Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Huntington Disease</term><term>Motor Neuron Disease</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genetic Testing</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Disease Progression</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>Linear Models</term><term>Middle Aged</term><term>Neuropsychological Tests</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The Unified Huntington's Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene-expanded participants from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntington's disease research and the planning of clinical trials of efficacy are discussed.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">24150908</PMID><DateCreated><Year>2014</Year><Month>03</Month><Day>18</Day></DateCreated><DateCompleted><Year>2014</Year><Month>12</Month><Day>01</Day></DateCompleted><DateRevised><Year>2015</Year><Month>03</Month><Day>12</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>29</Volume><Issue>3</Issue><PubDate><Year>2014</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Tracking motor impairments in the progression of Huntington's disease.</ArticleTitle><Pagination><MedlinePgn>311-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.25657</ELocationID><Abstract><AbstractText>The Unified Huntington's Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene-expanded participants from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntington's disease research and the planning of clinical trials of efficacy are discussed.</AbstractText><CopyrightInformation>© 2013 International Parkinson and Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Long</LastName><ForeName>Jeffery D</ForeName><Initials>JD</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paulsen</LastName><ForeName>Jane S</ForeName><Initials>JS</Initials></Author><Author ValidYN="Y"><LastName>Marder</LastName><ForeName>Karen</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Ying</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Ji-In</ForeName><Initials>JI</Initials></Author><Author ValidYN="Y"><LastName>Mills</LastName><ForeName>James A</ForeName><Initials>JA</Initials></Author><Author ValidYN="Y"><CollectiveName>Researchers of the PREDICT-HD Huntington's Study Group</CollectiveName></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>1U01NS082083</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>1U01NS082085</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>1U01NS082086</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>2 UL1 TR000442-06</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>5R01NS054893</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS040068</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>10</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Neurology. 2000 Jan 25;54(2):452-8</RefSource><PMID Version="1">10668713</PMID></CommentsCorrections><CommentsCorrections 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