Longitudinal analysis of neuropsychiatric symptoms in a large cohort of early-moderate manifest Huntington's disease patients

Background: The relationship between neuropsychiatric symptoms (NPS) and other clinical dimensions in Huntington's disease (HD) is controversial. This longitudinal study analyzed the association between NPS and motor, cognitive and functional aspects of the disease along with other variables related to its clinical onset and progression.Methods: 639 early-moderate HD patients were assessed longitudinally (mean: 4.95 visits/5 years). Generalized linear mixed models were used to explore associations between NPS and the aforementioned aspects. Other variables previously reported as significant in smaller or cross-sectional studies were included in the models.Results: Significant associations found included a negative linear relationship between presence of depressed mood and illness duration (7.2% odds reduction of being depressed per year), a 7.6% increase in the odds of having irritability with increased chorea scores, a negative association (4.3% reduction in odds) between age at onset and aggression (i.e. earlier onset was related to a higher probability of having aggressive behaviors) and a negative association between irritability and the interference component of the Stroop test (3% odds change). Total functional capacity (TFC) was the most frequently associated factor with NPS, with apathy and persev-erative behavior having the strongest relations with TFC (22% and 18% increases in odds per unit reduction in TFC respectively).Conclusions: With the exception of irritability, NPS are not related to motor or cognitive variables in early -moderate HD. Total functional capacity (TFC) is the most frequently associated factor with NPS, with apathy and perseverative behavior having the strongest relations with TFC.