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Tracking motor impairments in the progression of Huntington's disease
Movement disorders, 2014-03, Vol.29 (3), p.311-319
Long, Jeffery D.
Paulsen, Jane S.
Marder, Karen
Zhang, Ying
Kim, Ji-In
Mills, James A.
2014
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Long, Jeffery D.
Paulsen, Jane S.
Marder, Karen
Zhang, Ying
Kim, Ji-In
Mills, James A.
Titel
Tracking motor impairments in the progression of Huntington's disease
Ist Teil von
Movement disorders, 2014-03, Vol.29 (3), p.311-319
Ort / Verlag
United States: Blackwell Publishing Ltd
Erscheinungsjahr
2014
Quelle
MEDLINE
Beschreibungen/Notizen
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. © 2013 International Parkinson and Movement Disorder Society
Sprache
Englisch
Identifikatoren
ISSN: 0885-3185
eISSN: 1531-8257
DOI: 10.1002/mds.25657
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4219558
Format
–
Schlagworte
Adult
,
Aged
,
cohort studies
,
Disease Progression
,
Genetic Predisposition to Disease
,
Genetic Testing - methods
,
Humans
,
Huntington Disease - diagnosis
,
Huntington Disease - genetics
,
Huntington's disease
,
Linear Models
,
Middle Aged
,
Motor Neuron Disease - diagnosis
,
Motor Neuron Disease - genetics
,
Movement disorders
,
neurodegenerative disease
,
Neuropsychological Tests
,
predictive testing
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