Early weight instability is associated with cognitive decline and poor survival in amyotrophic lateral sclerosis

Abstract

Objective: Our aim was to measure the monthly rate of weight loss during 6 months prior to a diagnosis of amyotrophic lateral sclerosis (ALS) and to explore the effect on prognosis.

Methods: We enrolled 522 patients free from eating difficulties and with short diagnostic delay between June 2014 to June 2019. The calculating formula for the monthly rate of weight loss=[(weight at baseline-weight at diagnosis)/(weight at baseline*100 %)]/time interval. We employed logistic regression analysis to reveal any association between weight loss and cognitive dysfunction. Survival analysis was performed using the Kaplan-Meier curves and Cox proportional hazard models.

Results: Weight loss was observed in 272 patients (52.1 %). Patients with severe weight loss had an older age of onset, a lower ALS Functional Rating Scale-Revised score, a faster disease progression rate, and higher frequencies of executive dysfunction and cognitive decline. The monthly rate of weight loss was associated with executive dysfunction and cognitive decline after adjusting for the emotional state. The stratified monthly rate of weight loss was strongly and independently related to ALS survival after adjusting for confounding factors (HR = 1.473, P trend<0.001). Each upper ladder of the rate of weight loss was correlated with worse survival and a 47.3 % (95 % CI: 25.0-73.6 %) increased risk of mortality.

Conclusions: Weight loss is very common in patients with ALS and is associated with poor survival. It is also associated with executive dysfunction and cognitive decline. An important mechanism of weight loss in the early stage of this disease may be hypermetabolism.

Keywords: Amyotrophic lateral sclerosis; Cox analysis; Prognosis; Register study; Weight loss.