The timing and impact of psychiatric, cognitive and motor manifestations of Huntington’s disease

Abstract Objective To assess the prevalence, timing and functional impact of psychiatric, cognitive and motor manifestations of Huntington’s disease (HD), we analysed retrospective clinical data from individuals with manifest HD. Methods The clinical manifestations of HD were analysed for 6316 individuals in the European REGISTRY study from 161 sites across 17 countries. Data came from clinical history and the Clinical Characteristics Questionnaire that assessed eight symptoms: motor, cognitive, apathy, depression, perseverative/obsessive behavior, irritability, violent/aggressive behavior, and psychosis. Multiple logistic regression was used to analyse 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. The nature of the first manifestation is not associated with pathogenic CAG repeat length. Symptom prevalence data from the patient-completed Clinical Characteristics Questionnaire correlate specifically with validated clinical measures. Using these data, we show that psychiatric and cognitive symptoms are common in HD, with earlier onsets associated with longer CAG repeats. 42.4% of HD patients reported at least one psychiatric or cognitive symptom before motor onset, with depression most common. Apathy and cognitive impairment tend to come later in the disease course. Each psychiatric or cognitive manifestation of HD was associated with significantly reduced total functional capacity scores. Conclusions Psychiatric and cognitive symptoms occur before motor onset in many more HD patients than previously reported. They have a greater negative impact on daily life than involuntary movements and should be specifically targeted with clinical outcome measures and treatments.