Effect of Environmental Personal Exposure on Amyotrophic Lateral Sclerosis Disease Progression

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor function decline, although its etiology remains unclear. This study investigates the potential effect of air pollution and weather factors on ALS progression, using Non-Invasive Ventilation (NIV), Percutaneous Endoscopic Gastrostomy (PEG), and death as clinical endpoints. ALS clinical data from the H2020 BRAINTEASER project were used, including demographic and clinical information recorded at disease onset, and dynamic assessments of disease progression, represented by subscores of various functional domains, recorded at follow-ups. Air pollution data were sourced from the European Air Quality Portal, selecting pollutants based on the World Health Organization's air quality guidelines, while weather parameters were obtained from the European Climate Assessment Dataset. An Inverse Distance Weighting algorithm was applied to interpolate environmental data, which were then matched to patient residence postcode. To explore the effects of environmental exposure on clinical endpoints (NIV, PEG, and death), Cox Regression models with stepwise feature selection were applied using two analytical setups: (a) a cross-sectional snapshot of patients' clinical and environmental conditions at baseline; (b) a longitudinal exposure over the first year following baseline, where multivariable environmental exposure trajectories were computed using Topological Data Analysis (TDA). Cox Regression models incorporating clinical and environmental variables demonstrated comparable or higher predictive performances, measured by the Concordance Index (C-Index), compared to models based solely on clinical variables. Moreover, TDA trajectories revealed significant associations between multivariable exposure patterns and ALS progression, highlighting a potential joint effect of air pollution and weather factors.