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 and pneumonia that contribute to 26% of ALS mortality. The current proposal is strongly motivated by fundamental knowledge gaps that have contributed to sub-optimal clinical care of individuals with ALS and a lack of formal practice guidelines in the management of progressive swallowing impairment in ALS. The overarching goal of this work is to improve clinical practice by 1) increasing our understanding of governing mechanisms and progression of dysphagia in ALS and 2) identification of sensitive biomarkers of swallowing dysfunction to build a clinical dysphagia risk index tool. We will perform serial instrumental swallowing evaluations in 100 individuals with ALS (50 bulbar-onset, 50 spinal-onset) from disease diagnosis to feeding-tube dependence 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, for planning and design of future clinical trials, and for 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.

Public Health Relevance

The proposed study is relevant to public health as it will deliver new insights into the pathophysiologic mechanisms of swallowing decline in amyotrophic lateral sclerosis (ALS) and drive the development of future therapeutic strategies. It will also produce a highly practical and novel clinical assessment tool to facilitate earlier detection and accurate monitoring of swallowing function that has potential application to other patient populations also suffering from dysphagia. Earlier identification and better treatment strategies for swallowing dysfunction in ALS will lead to improvements in quality of life and reductions in individual health care costs, caregiver burden, malnutrition and dehydration, aspiration pneumonia and ultimately mortality in this disease population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS100859-03
Application #
9660610
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Gubitz, Amelie
Project Start
2017-04-01
Project End
2022-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Florida
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611