Timing and Impact of Psychiatric, Cognitive, and Motor Abnormalities in Huntington Disease

Neurology. 2021 May 11;96(19):e2395-e2406. doi: 10.1212/WNL.0000000000011893. Epub 2021 Mar 25.


Objective: To assess the prevalence, timing, and functional impact of psychiatric, cognitive, and motor abnormalities in Huntington disease (HD) gene carriers, we analyzed retrospective clinical data from individuals with manifest HD.

Methods: Clinical features of patients with HD were analyzed for 6,316 individuals in an observational study of the European Huntington's Disease Network (REGISTRY) from 161 sites across 17 countries. Data came from clinical history and the patient-completed Clinical Characteristics Questionnaire that assessed 8 symptoms: motor, cognitive, apathy, depression, perseverative/obsessive behavior, irritability, violent/aggressive behavior, and psychosis. Multiple logistic regression was used to analyze relationships between symptoms and functional outcomes.

Results: The initial manifestation of HD is increasingly likely to be motor and less likely to be psychiatric as age at presentation increases and is independent of pathogenic CAG repeat length. The Clinical Characteristics Questionnaire captures data on nonmotor symptom prevalence that correlate specifically with validated clinical measures. Psychiatric and cognitive symptoms are common in HD gene carriers, with earlier onsets associated with longer CAG repeats. Of patients with HD, 42.4% reported at least 1 psychiatric or cognitive symptom before motor symptoms, with depression most common. Each nonmotor symptom was associated with significantly reduced total functional capacity scores.

Conclusions: Psychiatric and cognitive symptoms are common and functionally debilitating in HD gene carriers. They require recognition and targeting with clinical outcome measures and treatments. However, because it is impossible to distinguish confidently between nonmotor symptoms arising from HD and primary psychiatric disorders, particularly in younger premanifest patients, nonmotor symptoms should not be used to make a clinical diagnosis of HD.

Trial registration information: ClinicalTrials.gov Identifier: NCT01590589.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology*
  • Cognition Disorders / psychology
  • Female
  • Humans
  • Huntington Disease / diagnosis
  • Huntington Disease / epidemiology*
  • Huntington Disease / psychology
  • Internationality*
  • Male
  • Mental Disorders / diagnosis
  • Mental Disorders / epidemiology*
  • Mental Disorders / psychology
  • Middle Aged
  • Motor Skills Disorders / diagnosis
  • Motor Skills Disorders / epidemiology*
  • Motor Skills Disorders / psychology
  • Neuropsychological Tests*
  • Retrospective Studies
  • Time Factors

Associated data

  • ClinicalTrials.gov/NCT01590589