Funding agencies: This research is supported by the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke (NS040068), the CHDI Foundation, Inc. (A3917), Cognitive and Functional Brain Changes in Preclinical Huntington's Disease (HD) (5R01NS054893), 4D Shape Analysis for Modeling Spatiotemporal Change Trajectories in Huntington's (1U01NS082086), Functional Connectivity in Pre-manifest Huntington's Disease (1U01NS082083), and Basal Ganglia Shape Analysis and Circuitry in Huntington's Disease (1U01NS082085). The publication was supported by the National Center for Advancing Translational Sciences and the NIH through grant 2 UL1 TR000442-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Tracking motor impairments in the progression of Huntington's disease
Article first published online: 21 OCT 2013
© 2013 International Parkinson and Movement Disorder Society
Volume 29, Issue 3, pages 311–319, March 2014
How to Cite
Long, J. D., Paulsen, J. S., Marder, K., Zhang, Y., Kim, J.-I., Mills, J. A. and the Researchers of the PREDICT-HD Huntington's Study Group (2014), Tracking motor impairments in the progression of Huntington's disease. Mov. Disord., 29: 311–319. doi: 10.1002/mds.25657
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 17 MAR 2014
- Article first published online: 21 OCT 2013
- Manuscript Accepted: 31 JUL 2013
- Manuscript Revised: 23 JUL 2013
- Manuscript Received: 3 MAY 2013
- movement disorders;
- Huntington's disease;
- neurodegenerative disease;
- predictive testing;
- cohort studies
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