title: Natural history of Huntington disease.
abstract: OBJECTIVE
  Understanding the natural history of Huntington disease will inform patients and clinicians on the disease course and researchers on the design of clinical trials.
  
  
  OBJECTIVE
  To determine the longitudinal change in clinical features among individuals with Huntington disease compared with controls.
  
  
  METHODS
  Prospective, longitudinal cohort study at 44 research sites in Australia (n = 2), Canada (n =4), and the United States (n = 38). Three hundred thirty-four individuals with clinically manifest Huntington disease who had at least 3 years of annually accrued longitudinal data and 142 controls consisting of caregivers and spouses who had no genetic risk of Huntington disease.
  
  
  METHODS
  Change in movement, cognition, behavior, and function as measured by the Unified Huntington's Disease Rating Scale, the Mini-Mental State Examination, and vital signs.
  
  
  RESULTS
  Total motor score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by 0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (95% CI, 0.6-0.8) per year on the Mini-Mental State Examination. Behavior, as measured by the product of frequency and severity score on the Unified Huntington's Disease Rating Scale, worsened by 0.6 point per year (95% CI, 0.0-1.2). Total functional capacity declined by 0.6 point per year (95% CI, 0.5-0.7). Compared with controls, baseline body mass index was lower in those with Huntington disease (25.8 vs 28.8; P < .001), and average pulse was higher (74.2 vs 69.6 beats/min; P < .001).
  
  
  CONCLUSIONS
  Over 3 years, the cardinal features of Huntington disease all declined in a monotonic manner. These data quantify the natural history of the disease and may inform the design of trials aimed at reducing its burden.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00313495.
authors.affiliation: Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland6now with the University of Rochester Medical Center, Rochester, New York.
authors.forename: E Ray
authors.initials: ER
authors.lastname: Dorsey
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Beck
authors.affiliation: Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland.
authors.forename: Kristin
authors.initials: K
authors.lastname: Darwin
authors.affiliation: Department of Neurology, Johns Hopkins Medicine, Baltimore, Maryland.
authors.forename: Paige
authors.initials: P
authors.lastname: Nichols
authors.affiliation: Center for Human Experimental Therapeutics, University of Rochester Medical Center, Rochester, New York.
authors.forename: Alicia F D
authors.initials: AF
authors.lastname: Brocht
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Biglan
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC.
authors.forename: Ira
authors.initials: I
authors.lastname: Shoulson
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D002170:Canada; D003072:Cognition Disorders / Q000209:etiology*; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000150:complications*; D008297:Male; D001523:Mental Disorders / Q000209:etiology*; D008875:Middle Aged; D009069:Movement Disorders / Q000209:etiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D018911:Trinucleotide Repeats / Q000235:genetics; D014481:United States
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins