Tracking Motor Impairments in the Progression of Huntington’s Disease

Jeffery D Long; Jane S Paulsen; Karen Marder; Ying Zhang; Ji-In Kim; James A Mills; Researchers PREDICT-HD Huntingtons

doi:10.1002/mds.25657

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Tracking Motor Impairments in the Progression of Huntington’s Disease

Journal article

Open access

Peer reviewed

Tracking Motor Impairments in the Progression of Huntington’s Disease

Jeffery D Long, Jane S Paulsen, Karen Marder, Ying Zhang, Ji-In Kim, James A Mills and Researchers PREDICT-HD Huntingtons

Movement disorders, Vol.29(3), pp.311-319

03/2014

DOI: 10.1002/mds.25657

PMCID: PMC4219558

PMID: 24150908

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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.

cohort studies

Huntington’s disease

neurodegenerative disease

movement disorders

predictive testing

Details

Title: Subtitle: Tracking Motor Impairments in the Progression of Huntington’s Disease
Creators: Jeffery D Long - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Jane S Paulsen - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Karen Marder - Departments of Neurology and Psychiatry, Sergievsky Center and Taub Institute, College of Physicians and Surgeons, Columbia University, New York, New York, USA
Ying Zhang - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA
Ji-In Kim - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
James A Mills - Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Researchers PREDICT-HD Huntingtons
Resource Type: Journal article
Publication Details: Movement disorders, Vol.29(3), pp.311-319
DOI: 10.1002/mds.25657
PMID: 24150908
PMCID: PMC4219558
NLM abbreviation: Mov Disord
ISSN: 0885-3185
eISSN: 1531-8257
Language: English
Date published: 03/2014
Academic Unit: Psychiatry; Psychological and Brain Sciences; Biostatistics
Record Identifier: 9984083299702771

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