Exploring Constipation as a Mediator in the Association Between Amyotrophic Lateral Sclerosis Progression and Survival: A Multicenter Prospective Cohort Study

Introduction: As a rare neurodegenerative disease, the prognosis of Amyotrophic lateral sclerosis (ALS) is closely linked to motor symptoms. Recent research has increasingly concentrated on non-motor symptoms (NMS), especially constipation, and their correlation with survival in patients with ALS. However, it is unclear whether there is an interaction and/or mediation effect between NMS, especially constipation, and ALS progression and survival. Therefore, this study aims to investigate the role of NMS in the relationship between ALS progression and survival. Methods: We conducted a multicenter prospective cohort study on ALS patients. Based on the inclusion and exclusion diagnoses, we collected a total of 150 ALS patients and conducted a nine-month follow-up. Results: We applied the VanderWeele's Four-Way Decomposition method to decompose the excess risk of moderate (ΔFS: 0.47-1.1/month)/fast (ΔFS>1.1/month) ALS progression compared to slow (ΔFS<0.47/month) ALS progression into four components. The results indicated that the interaction effect between constipation and the progression rate of ALS (moderate/severe) played a significant role, with values of 2.571 and 10.819, accounting for 81.890% and 91.590% of the total increased excess risk, respectively (P<0.05). Conclusions: Our results suggest that constipation plays an interaction role between ALS progression and survival. Clinical Trial Registration number: ChiCTR2500101119. The registration time is 21/04/2025.