Objective: Refine understanding of the processes underpinning apathy in neurodegenerative disease, by identifying 1) objective measures to assess apathy; 2) parcellating the broad construct of apathy into sub-components.

Background: Apathy is pervasive in neurodegenerative disease. Defined as a loss of motivation, currently little progress has been made to identify the cognitive and neural substrates that underpin this broad construct. Establishing objective measures to assess apathy and identifying its sub-processes will be critical to advancing our knowledge of the neural systems involved and to promote novel drug therapies.

Methods: In a cohort of Parkinson’s disease (PD) and Huntington’s disease (HD) patients we administered a battery of novel tasks to measure causal components involved in apathy, including reward sensitivity, willingness to exert effort and reinforcement learning. Questionnaire assessment of everyday apathy, mood and impulsivity was also included.

Results: Key preliminary results include strong correlations between extent of everyday apathy severity in HD and reduced effort on a novel translational Progressive Ratio task (r=.6, p<.01). In PD patients, higher levels of apathy were associated with increased loss aversion on a reinforcement learning task (r=.5, p<.05) and higher apathy severity in daily life was associated with a more conservative strategy on a novel betting task, consistent with reduced reward sensitivity. Extensions to the current analyses include computational modelling of the data and factor analysis to determine apathy sub-types.

Conclusions: We identify relationships between novel, objective apathy assessments and apathy severity in daily life. Differential involvement of reward processing and effort-maintenance neural systems is implicated. These results will offer new insight into the multidimensional nature of apathy in neurodegenerative disease, and provide a crucial link between the everyday behavioural symptoms of apathy and their underlying neurocognitive substrates.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/fractionating-apathy-effort-reward-and-impulsivity-mechanisms-in-parkinsons-and-huntingtons-disease/