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J Neurol. 2015 Dec;262(12):2691-8. doi: 10.1007/s00415-015-7900-7. Epub 2015 Sep 26.

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

Author information

1
Department of Psychiatry, Carver College of Medicine, The University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA.
2
Biogen, 300 Binney Street, Cambridge, MA, 02142, USA.
3
Department of Biostatistics, College of Public Health, The University of Iowa, S160 CPHB, 145 N. Riverside Drive, Iowa City, IA, 52242, USA.
4
Department of Biostatistics, Indiana University Fairbanks School of Public Health, 410 W. Tenth Street, Suite 3000, Indianapolis, IN, 46202, USA.
5
Department of Psychiatry and Brain Research Centre, University of British Columbia, Detwiller Pavilion, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada.
6
Department of Neurology, Gertrude H. Sergievsky Center, Taub Institute on Alzheimers Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, 710 West 168th Street, New York, NY, 10032, USA.
7
Department of Psychiatry, Columbia University Medical Center, 622 West 168th Street, New York, NY, 10032, USA.
8
Institute for Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Maindy Road, Cathays, Cardiff, CF24 4HQ, UK.
9
School of Biosciences, Cardiff University, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, UK.
10
Department of Neurology, Westmead Hospital, The University of Sydney, Cnr Hawkesbury and Darcy Roads, Westmead, NSW, 2145, Australia.
11
Department of Psychiatry, Carver College of Medicine, The University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA. predict-publications@uiowa.edu.
12
Department of Neurology, Carver College of Medicine, The University of Iowa, 2007 Roy Carver Pavilion, 200 Hawkins Drive, Iowa City, IA, 52242, USA. predict-publications@uiowa.edu.
13
Department of Psychology, The University of Iowa, E11 Seashore Hall, Iowa City, IA, 52242, USA. predict-publications@uiowa.edu.

Abstract

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.

KEYWORDS:

Diagnosis; Diagnostic confidence level; Hidden Markov model; Huntington disease; Onset; Prediction

PMID:
26410751
PMCID:
PMC4666501
DOI:
10.1007/s00415-015-7900-7
[Indexed for MEDLINE]
Free PMC Article

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