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

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.
Competing Interests: Author VS received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., and Novartis Pharma AG, received research supports from the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call, and was in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology. Authors BP and LC received compensation for consulting services and/or speaking activities from Liquidweb S.r.l. Author NT received compensation for consulting services from Amylyx Pharmaceuticals and Zambon Biotech SA. Author FSq received compensation for consulting services and/or speaking activities from La Hoffman-Roche, Novartis, PTC Therapeutics, Wave Life Science, Prilenia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Poletti, Solca, Maffi, Torre, Carelli, Aiello, Ferrucci, Priori, Monti, Verde, Ticozzi, Migliore, Scaricamazza, Casella, Squitieri, Ciammola and Silani.)