Quality of life and disability in pure autonomic failure: More than a prodromal synucleinopathy

Introduction: Pure autonomic failure (PAF) is a neurodegenerative disease that leads to widespread autonomic dysfunction. To date, no studies have specifically assessed health-related quality of life (HRQoL) and disability in PAF patients. Methods: We performed a cross-sectional study involving 30 PAF patients from the “IAF-BO cohort”. HRQoL was measured using 36-item Short-form Health Survey (SF-36) and disability using activities of daily living (ADL), instrumental ADL (IADL), and modified Barthel Index (mBI). Associations were evaluated between clinical features, autonomic symptoms, HRQoL and disability. Results: HRQoL in PAF patients was significantly lower than in general population, particularly in physical health domains of SF-36. Half of the participants showed mild dependence in ADL, IADL and mBI, with urinary control being the most affected function. Strong associations were identified between the SF-36 physical component score and autonomic symptoms, while no associations were observed with disease duration or depression. Significant associations also emerged between disability measures and autonomic symptoms. Additionally, resilience showed a significant interaction effect with autonomic symptoms in the regression model, where lower resilience was associated with higher disability. Conclusion: This is the first study to evaluate HRQoL, disability and their relations with autonomic dysfunctions in PAF. While PAF is typically considered a prodromal α-synucleinopathy, our findings demonstrated that it is indeed a disabling disease that significantly impacts both quality of life and functional independence. These results underscore the need for targeted pharmacological interventions to improve the lives of individuals affected by PAF.