Constipation modifies the association between disease progression and survival in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, and its prognosis is closely associated with the rate of disease progression. An increasing number of studies are focusing on non-motor symptoms (NMS), particularly constipation; however, their role in the association between ALS progression and survival remains unclear. This study investigated the contribution of NMS to the relationship between ALS progression and survival. In this multicenter prospective cohort study, 150 patients with ALS were followed for 9 months. VanderWeele’s four-way decomposition method was applied to evaluate the interaction and mediation effects of NMS on the association between ALS progression and survival. Compared with slow progression (ΔFS < 0.47/month), moderate progression (ΔFS 0.47–1.1/month) and fast progression (ΔFS > 1.1/month) were associated with increased excess relative risk of mortality. Constipation demonstrated significant interaction effects with ALS progression. The combined interaction components accounted for 79.55% and 91.15% of the excess relative risk in the moderate- and fast-progression groups, respectively. In contrast, no significant pure natural indirect effect was observed. Constipation primarily functions as an interacting factor rather than a mediator in the association between ALS progression and survival. These findings highlight the potential prognostic relevance of constipation, particularly among patients with more rapidly progressive disease.