Semiology and determinants of apathy across neurodegenerative motor disorders: A comparison between amyotrophic lateral sclerosis, Parkinson's and Huntington's disease

Front Aging Neurosci. 2022 Nov 2:14:1031908. doi: 10.3389/fnagi.2022.1031908. eCollection 2022.


Background: The semiology and determinants of apathy are largely unknown across amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD), due to both motor and non-motor confounders. This study thus aimed at (1) profiling apathy in ALS, PD, and HD and (2) exploring its clinical determinants.

Materials: Consecutive ALS (N = 99), PD (N = 73), and HD (N = 25) patients underwent a motor-free assessment of apathy (Dimensional Apathy Scale, DAS), global cognition, anxiety and depression. Function was assessed through disease-specific scales. The DAS was also completed by N = 101 healthy controls (HCs). Between-group comparisons on DAS scores were implemented by covarying for all applicable confounders. Predictive models on DAS scores were built through multiple, stepwise regressions.

Results: Parkinson's disease and HD, but not ALS, patients were more apathetic than HCs-with HD patients also selectively showing lower initiation and poorer goal-directed planning than HCs. Higher apathetic features were detected in PD and HD as compared to ALS. Education was a protective factor against apathy in ALS. Anxiety was a risk factor for global apathy in ALS, HD, and to a lesser extent, in PD, whereas, protective only toward affective disintegration in PD and ALS. Cognitive inefficiency was a risk factor toward apathy in both PD and ALS. Depression was a risk factor for executive-related apathy in PD.

Discussion: This study provides unprecedented insights into the heterogeneous semiology and determinants of apathy across ALS, PD, and HD via the DAS, in turn informing clinical practice and research.

Keywords: Huntington’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; apathy; neuropsychology.