Journal of Neurology

, Volume 262, Issue 12, pp 2691–2698 | Cite as

Motor onset and diagnosis in Huntington disease using the diagnostic confidence level

  • Dawei Liu
  • Jeffrey D. Long
  • Ying Zhang
  • Lynn A. Raymond
  • Karen Marder
  • Anne Rosser
  • Elizabeth A. McCusker
  • James A. Mills
  • Jane S. Paulsen
  • The PREDICT-HD Investigators and Coordinators of the Huntington Study Group
Original Communication


Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine–adenine–guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington’s Disease Rating Scale. HD progression from unimpaired to impaired motor function, as well as the progression from motor impairment to diagnosis, was associated with the linear effect of age and CAG repeat length. Specifically, for every 1-year increase in age, the risk of transition in diagnostic confidence level increased by 11 % (95 % CI 7–15 %) and for one repeat length increase in CAG, the risk of transition in diagnostic confidence level increased by 47 % (95 % CI 27–69 %). Findings show that CAG repeat length and age increased the likelihood of the first onset of motor impairment as well as the age at diagnosis. Results suggest that more accurate estimates of HD onset age can be obtained by incorporating the current status of diagnostic confidence level into predictive models.


Huntington disease Hidden Markov model Diagnostic confidence level Prediction Diagnosis Onset 

Supplementary material

415_2015_7900_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Dawei Liu
    • 1
    • 2
  • Jeffrey D. Long
    • 1
    • 3
  • Ying Zhang
    • 4
  • Lynn A. Raymond
    • 5
  • Karen Marder
    • 6
    • 7
  • Anne Rosser
    • 8
    • 9
  • Elizabeth A. McCusker
    • 10
  • James A. Mills
    • 1
  • Jane S. Paulsen
    • 1
    • 11
    • 12
  • The PREDICT-HD Investigators and Coordinators of the Huntington Study Group
  1. 1.Department of PsychiatryCarver College of Medicine, The University of IowaIowa CityUSA
  2. 2.BiogenCambridgeUSA
  3. 3.Department of BiostatisticsCollege of Public Health, The University of Iowa, S160 CPHBIowa CityUSA
  4. 4.Department of BiostatisticsIndiana University Fairbanks School of Public HealthIndianapolisUSA
  5. 5.Department of Psychiatry and Brain Research CentreUniversity of British ColumbiaVancouverCanada
  6. 6.Department of Neurology, Gertrude H. Sergievsky Center, Taub Institute on Alzheimers Disease and the Aging BrainColumbia University College of Physicians and SurgeonsNew YorkUSA
  7. 7.Department of PsychiatryColumbia University Medical CenterNew YorkUSA
  8. 8.Institute for Psychological Medicine and Clinical NeurosciencesCardiff University School of MedicineCardiffUK
  9. 9.School of BiosciencesCardiff UniversityCardiffUK
  10. 10.Department of NeurologyWestmead Hospital, The University of SydneyWestmeadAustralia
  11. 11.Department of Neurology, Carver College of MedicineThe University of IowaIowa CityUSA
  12. 12.Department of PsychologyThe University of IowaIowa CityUSA

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