Weight Loss and Disease Progression in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis (P2-8.009)

Abstract

<h3>Objective:</h3> We studied the association of changes in body mass index (BMI) with disease progression among amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) Multicenter Cohort Study of Oxidative Stress (COSMOS) study participants, prospectively followed up to 24 months. <h3>Background:</h3> Weight loss is a poor prognostic factor in ALS. However, less is known about weight change in PLS. <h3>Design/Methods:</h3> Participants had a confirmed diagnosis of ALS or PLS and completed baseline and at least one follow-up visit. The rate of BMI change (ΔBMI) and total revised ALS functional rating scale change (ΔALSFRS-r) were calculated between baseline and the first follow-up. Correlation between ΔBMI and ΔALSFRS-r were assessed using Pearson correlation among ALS and PLS participants separately. The demographics and proportion of participants with swallowing dysfunction at baseline and significant weight loss were compared between ALS and PLS groups using chi-square test. Cox proportional hazard models examined the association between significant weight loss (ΔBMI&lt;−1kg/m2/year) and survival in ALS, adjusted for other prognostic factors. <h3>Results:</h3> 279 ALS and 37 PLS participants were included. Mean age of ALS and PLS were both 60 years and 61% male. At baseline, swallowing dysfunction was more frequent in the PLS (78% vs 48%, p&lt;0.001) while significant weight loss was more frequent in the ALS (53% vs 19%, p&lt;0.001). ΔBMI and ΔALSFRS-r correlated significantly in ALS (r=0.3, p&lt;0.0001) but not in PLS (r= −0.21, p=0.2). Significant weight loss was associated with increased risk of death (hazard ratio 2.08, p&lt;0.0001) in ALS after adjusting for age, disease-duration, bulbar-onset, diagnostic-certainty, riluzole-intake, forced vital capacity, baseline BMI, baseline ALSFRS-r and ΔALSFRS-r. <h3>Conclusions:</h3> In ALS, significant weight loss is a strong independent prognostic factor for survival and rate of BMI change correlates with faster functional decline. In contrast, significant weight loss is infrequent in PLS despite a high prevalence of swallowing dysfunction. <b>Disclosure:</b> Dr. Lee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Lee has received personal compensation in the range of $0-$499 for serving as a Consultant for Amylyx. Dr. Lee has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Regeneron. The institution of Dr. Lee has received research support from Myasthenia Gravis Foundation of America. The institution of Dr. Lee has received research support from CReATe consortium/American Brain Foundation. Dr. Mitsumoto has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Pam Factor-Litvak has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ICF. Pam Factor-Litvak has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Publishing. The institution of Pam Factor-Litvak has received research support from NIH. Prof. Nieves has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Bone Health and Osteoporosis Foundation. The institution of Prof. Nieves has received research support from Radius Pharmaceuticals. Prof. Nieves has received personal compensation in the range of $0-$499 for serving as a DSMB member with NIH.