F22 Novel measures of apathy in huntington’s disease: cross-sectional and longitudinal analysis

Background Apathy is a core symptom of Huntington’s Disease (HD), appearing up to 10 years before the onset of motor symptoms and worsening alongside disease progression. Research into the disease needs greater focus on this symptom, but to date, limited tools exist for measuring apathy in HD. Aims This study aimed to evaluate the longitudinal validity and sensitivity of two novel computer tasks that were designed to measure apathy in HD, to assess their potential for future use in clinical trials. Method A total of 83 individuals with HD and 54 controls underwent extensive testing on a battery of existing and novel tasks that measured a range of deficits in HD. Included in this battery were the two novel tasks, the Persistence task and the Maze task, as well as the current gold-standard measures: the Problem Behaviours Assessment Scale of apathy (PBA-apathy) and the Composite Unified Huntington’s Disease Rating scale (cUHDRS). Participants were tested on the entire battery at baseline and at 12-month follow up. Results Both the Maze and Persistence tasks were able to distinguish gene positive participants from controls, but only the Maze task was found to be sensitive to change between baseline and follow up. Moreover, it appeared to be more sensitive than the cUHDRS, which did not show significant change over 12 months in this population. However, the Maze task did not show association with PBA-apathy scores, suggesting it does not measure core elements of apathy as defined by the PBA. The Persistence task was associated with PBA-apathy at baseline, but this association did not persist to follow up, suggesting that the task lacks longitudinal validity. Conclusion This study highlights the potential utility of objective computer tasks in HD research, reducing the field’s reliance on subjective self-report measures. Excitingly the findings also suggest that the Maze task could become a new objective measure of disease progression, superior to existing tools.