Functional status, depressive symptoms, sleep quality and fatigue in amyotrophic lateral sclerosis: a mediation analysis

Fatigue is a prevalent and disabling symptom in amyotrophic lateral sclerosis (ALS). This study investigated the factors contributing to fatigue severity and explored the mediating effects of sleep quality and depressive symptoms. A cross-sectional study was conducted on 207 patients with ALS. Fatigue was assessed using the Fatigue Severity Scale (FSS). Functional status, sleep quality, depressive symptoms, and pulmonary function were measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9), and spirometry-derived forced vital capacity percentage (FVC%), respectively. Spearman correlation, multiple linear regression, and bootstrap-based mediation analyses were performed, with age and BMI included as covariates. Fatigue severity varied significantly with age, BMI, and FVC% (all p < 0.05). Fatigue correlated negatively with ALSFRS-R (r = -0.448) and FVC% (r = -0.321), and positively with PSQI (r = 0.335) and PHQ-9 (r = 0.324) (all p < 0.001). Regression analysis revealed ALSFRS-R (β = -0.219), PSQI (β = 0.167), PHQ-9 (β = 0.177), and FVC% (β = -0.158) as independent factors (all p < 0.05). Mediation analyses demonstrated that PSQI and PHQ-9 partially mediated the association between ALSFRS-R and fatigue (total indirect effect = -0.1012, an estimated 16.67% of the total effect). No significant mediation was observed in the FVC%–fatigue pathway. Fatigue in ALS was associated with functional impairment, poor sleep, depressive symptoms, and reduced pulmonary function. Sleep disturbance and depression partially mediated the relationship between functional status and fatigue, highlighting potential factors for comprehensive assessment and future intervention studies.