Abstract Details

Title Sex-related Differences in ALS Survival and Progression: Insights from a Population-based Study

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 11-004

Objective This study aimed to investigate sex-related differences in Amyotrophic Lateral Sclerosis (ALS) prognosis and identify potential contributing factors.

Background ALS is a neurodegenerative disease characterized by known disparities in prevalence rates and differences in the age and site of disease onset between males and females. However, the intricate relationship between sex, disease progression, and underlying mechanisms in ALS remains incompletely understood.

Design/Methods We obtained data from the population-based Piemonte and Valle d'Aosta Register for ALS (PARALS) and used the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database as a replication cohort. Survival analyses, stratified by the site of disease onset, were conducted to assess sex-related differences in survival. Disease progression was evaluated using the multidomain ALS Functional Rating Scale-Revised (ALSFRS-R) scores. Additionally, we explored the roles of Forced Vital Capacity (FVC) and weight decline through causal mediation analysis.

Results Males exhibited shorter survival when stratified by disease onset site (spinal onset: HR 1.143, 95%CI 1.04-1.257, P=0.0057; bulbar onset: HR 1.15, 95%CI 1.015-1.303, P=0.0284). Intriguingly, males did not experience faster disease progression; instead, women showed a more pronounced functional decline (+0.05 ALSFRS-R points per month, 95%CI 0.04-0.06, P<0.0001). Conversely, men exhibited worse respiratory decline (FVC% -4.2, 95%CI -6.3 to -2.2, P<0.0001) and faster weight loss (Kg lost per month -0.15, 95%CI -0.25 to -0.05, P=0.0030) already at diagnosis. Causal mediation analysis demonstrated that respiratory function and weight loss played pivotal roles in sex-related survival disparities. Analysis of the PRO-ACT cohort confirmed these trends.

Conclusions This comprehensive study reveals the interplay between sex, survival, and disease progression in ALS. The observed shorter survival in males is not directly linked to faster disease progression but is instead associated with respiratory function and weight loss. These findings underscore the importance of considering sex-specific factors in understanding ALS pathophysiology and designing tailored therapeutic strategies for this devastating disease.

Authors/Disclosures
Maurizio Grassano, MD (Dept. of Neuroscience, University of Turin) PRESENTER	Dr. Grassano has received research support from American Brain Foundation, ALS Association and ��ɫ��.
Francesca Palumbo (University of Turin Department of Neurosciences: Universita degli Studi di Torin)	Dr. Palumbo has nothing to disclose.
Cristina Moglia (University of Torino)	Cristina Moglia has nothing to disclose.
Paolina Salamone	No disclosure on file
Giuseppe Fuda	No disclosure on file
Rosario Vasta, MD (University of Turin, Department of Neurosciences)	Dr. Vasta has nothing to disclose.
Umberto Manera, MD (Department of Neuroscience "Rita Levi Montalcini" - University of Torino)	Dr. Manera has nothing to disclose.
Antonio Canosa	Antonio Canosa has nothing to disclose.
Federico Casale	No disclosure on file
Letizia Mazzini	No disclosure on file
Andrea Calvo, MD, PhD, FAAN (Dept. of Neuroscience, University of Turin)	Dr. Calvo has nothing to disclose.
Adriano Chio, MD, FAAN (Dept. of Neuroscience, University of Turin)	Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Corcept.

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