Sarcopenia in Amyotrophic Lateral Sclerosis: A Key Predictor of Respiratory Dysfunction and Disease Progression

Abstract

Background: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness and respiratory decline. Sarcopenia remains underexplored in terms of prevalence and their relationship with disease progression. We aimed to determine the prevalence of sarcopenia in ALS patients, assess the predictive value of morphofunctional assessment tools for sarcopenia, and explore their relationship with respiratory function and disease progression. Methods: A cross-sectional study was conducted with 40 ALS patients at the ALS Multidisciplinary Unit, San Cecilio University Hospital in Granada. Sarcopenia was defined based on the European Working Group of Sarcopenia in Older People 2(EWGSOP2) and malnutrition was diagnosed using GLIM criteria. Morphofunctional status was assessed using: Phase Angle(PA) and body composition by Bioelectrical Impedance Vector Analysis, muscle strength through Handgrip Strength (HGS). Respiratory function was evaluated using Forced Vital Capacity (FVC). Associations between sarcopenia, body composition, respiratory function, and disease severity were analyzed using logistic regression models. Receiver operating characteristic analyses were performed to identify optimal predictive cut-off values. Results: Sarcopenia was identified in 25% of ALS patients. Compared with non-sarcopenic individuals, sarcopenic patients exhibited significantly lower muscle mass indices, PA, and HGS, along with higher extracellular water percentage(%ECW). Malnutrition was more frequent in sarcopenia group (90%vs25%, p<0.001). Respiratory impairment was more pronounced in sarcopenic patients, with reduced FVC and elevated pCO₂ (p=0.02), and a greater need for non-invasive mechanical ventilation (NIMV) (70% vs. 10%, p=0.001). VC correlated positively with body cell mass index (BCMI) (r=0.450), skeletal muscle mass index (SMI) (r=0.413), and ALSFRS-R score (r =0.731; all p<0.05). Lower PA, BCMI, and ALSFRS-R scores, together with higher %ECW and partial pressure of carbon dioxide (pCO₂), predicted sarcopenia risk. Reduced BCMI, HGS, Short Physical Performance Battery (SPPB) and sarcopenia were associated with the need of NIMV. BCMI (cutoff:8.05 kg/m²;AUC:0.889) and ALSFRS-R (cut-off:33 points;AUC:0.884) were the most accurate predictors of sarcopenia and ventilatory support, respectively. Conclusions: This study is the first to assess sarcopenia prevalence in ALS patients using standardized diagnostic criteria. The findings highlight the relationship between sarcopenia, malnutrition, and respiratory decline. PA, BCMI, and respiratory parameters emerge as potential tools for sarcopenia and NIMV risk stratification.