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Timing and impact of psychiatric, cognitive, and motor abnormalities in Huntington disease

McAllister, Branduff, Gusella, James F., Landwehrmeyer, G. Bernhard, Lee, Jong-Min, MacDonald, Marcy E., Orth, Michael, Rosser, Anne E. ORCID:, Williams, Nigel M. ORCID:, Holmans, Peter ORCID:, Jones, Lesley ORCID: and Massey, Thomas H. ORCID: 2021. Timing and impact of psychiatric, cognitive, and motor abnormalities in Huntington disease. Neurology 96 (19) , e2395-e2406. 10.1212/WNL.0000000000011893

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Objective To assess the prevalence, timing and functional impact of psychiatric, cognitive and motor abnormalities in Huntington’s disease (HD) gene carriers, we analysed retrospective clinical data from individuals with manifest HD. Methods Clinical features of HD patients were analysed for 6316 individuals in the European REGISTRY study from 161 sites across 17 countries. Data came from clinical history and the patient-completed 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, and is independent of pathogenic CAG repeat length. The Clinical Characteristics Questionnaire captures data on non-motor 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. 42.4% of HD patients reported at least one psychiatric or cognitive symptom before motor symptoms, with depression most common. Each non-motor 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, as it is impossible to distinguish confidently between non-motor symptoms arising from HD and primary psychiatric disorders, particularly in younger pre-manifest patients, non-motor symptoms should not be used to make a clinical diagnosis of HD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: American Academy of Neurology
ISSN: 0028-3878
Funders: MRC
Date of First Compliant Deposit: 13 April 2021
Date of Acceptance: 12 February 2021
Last Modified: 05 May 2023 15:32

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