Project Summary Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing progressive muscle weakness and impairments in swallowing (dysphagia). Dysphagia leads to malnutrition, dehydration, tracheal aspiration, pneumonia, and death. The parent grant is strongly motivated by fundamental knowledge gaps that hinder clinical care of dysphagia in ALS. The overarching goal is to improve clinical practice by 1) increasing our understanding of governing mechanisms and progression rates of dysphagia in ALS, and 2) identification of sensitive clinical markers of dysphagia. We will perform serial instrumental swallowing evaluations in 100 individuals with ALS and provide critical longitudinal data to help establish the first time-course model of ALS swallowing decline. Such a model is needed to guide best practice recommendations, optimal timing of interventions, planning and design of future clinical trials, and interpretation of experimental treatment effects. We will also test the discriminant ability and clinical utility of a set of promising clinical markers of swallowing decline that are pragmatically designed for easy dissemination into ALS clinical settings. Our long-term goal is to improve clinical care of swallowing disorders in ALS. The proposed study will deliver new insights into the pathophysiologic mechanisms of unsafe and inefficient swallowing in ALS to drive the development of future intervention strategies and lead to earlier and more accurate identification of swallowing impairment. Earlier identification and better treatment strategies for swallowing dysfunction in ALS will lead to improvements in oral intake, nutrition, pulmonary health and quality of life, and ultimately reduce aspiration pneumonia associated mortality in this challenging population. This Landis Supplement Award will support the training and development of a post- doctoral fellow, who will work on this parent grant. It will additionally support trainee career development activities.