Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.26.116798v1?rss=1 Authors: McAllister, B., Gusella, J. F., Landwehrmeyer, G. B., Lee, J.-M., MacDonald, M. E., Orth, M., Rosser, A. E., Williams, N. M., REGISTRY Investigators of the European Huntingtons disease network,, Holmans, P., Jones, L., Massey, T. H. Abstract: BackgroundHuntingtons disease is characterised by a range of motor, psychiatric and cognitive symptoms. These present in different combinations through the disease course and impact on daily life and functioning. Huntingtons disease is caused by a dominant CAG repeat expansion in the HTT gene, and longer repeats are associated with earlier onset of motor symptoms. ObjectivesTo investigate the onset, prevalence and functional impact of motor and psychiatric symptoms of Huntingtons disease. MethodsWe analysed clinical phenotype data from the European REGISTRY study for 6316 individuals with manifest Huntingtons disease. Onset and prevalence data for motor and psychiatric symptoms were extracted from the clinical history part of REGISTRY and the detailed Clinical Characteristics Questionnaire. Generalised linear models were constructed to assess relationships between symptoms and functional outcomes. ResultsAs age at first presentation of Huntingtons disease increases, the likelihood that the initial presenting symptom is motor also increases. This is not associated with pathogenic CAG repeat length. At a population level there were conserved relationships between symptoms across different repeat lengths, with depression often occurring early followed by motor and then cognitive symptoms. There were significant relationships between all individual psychiatric and cognitive symptoms and reduced functional capacity. ConclusionsThere are conserved patterns of symptoms in HD that can be quantified. Psychiatric and behavioural symptoms significantly impair daily functioning and should be considered part of the disease trajectory at any age. Copy rights belong to original authors. Visit the link for more info