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, Stephen Cross, Patricia Ryan, Eric A. Epping, Stacie Vik, Edmond Chiu, Joy Preston, Anita Goh, Stephanie Antonopoulos, Samantha Loi, Phyllis Chua, Angela Komiti, Lynn Raymond, Joji Decolongon, Mannie FanAllison Coleman, Christopher A. Ross, Mark Varvaris, Nadine Yoritomo, William M. Mallonee, Greg Suter, Ali Samii, Alma Macaraeg, Randi Jones, Cathy Wood-Siverio, Stewart A. Factor, Roger A. Barker, Sarah Mason, Natalie Valle Guzman, Elizabeth McCusker, Jane Griffith, Clement Loy, David Gunn, Michael Orth, Sigurd Sübmuth, Katrin Barth, Sonja Trautmann, Daniela Schwenk, Carolin Eschenbach, Kimberly Quaid, Melissa Wesson, Joanne Wojcieszek, Mark Guttman, Alanna Sheinberg, Albie Law, Susan Perlman, Brian Clemente, Michael D. Geschwind, Sharon Sha, Gabriela Satris, Tom Warner, Maggie Burrows, Anne Rosser, Kathy Price, Sarah Hunt, Frederick Marshall, Amy Chesire, Mary Wodarski, Charlyne Hickey, Peter Panegyres, Joseph Lee, Maria Tedesco, Brenton Maxwell, Joel Perlmutter, Stacey Barton, Shineeka Smith, Zosia Miedzybrodzka, Daniela Rae, Mariella D'Alessandro, David Craufurd, Judith Bek, Elizabeth Howard, Pietro Mazzoni, Karen Marder, Paula Wasserman, Rajeev Kumar, Diane Erickson, Breanna Nickels, Vicki Wheelock, Lisa Kjer, Amanda Martin, Sarah Farias, Wayne Martin, Pamela King, Marguerite Wieler, Satwinder Sran, Oksana Suchowersky, Anwar Ahmed, Stephen Rao, Christine Reece, Alex Bura, Lyla Mourany, Jagan Pallai

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)311-319
Number of pages9
JournalMovement Disorders
Issue number3
StatePublished - Mar 2014
Externally publishedYes


  • Cohort studies
  • Huntington's disease
  • Movement disorders
  • Neurodegenerative disease
  • Predictive testing

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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