Croplands proximity is associated with amyotrophic lateral sclerosis incidence and age at onset

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from an intricate interplay between genetics and environmental factors. Many studies have explored living in rural areas as a possible risk factor for ALS, without focusing simultaneously on incidence, age at onset and phenotypic features. Objective: To evaluate the effect of croplands residential proximity on ALS incidence and phenotype, focusing on age of onset, site of onset and progression rate. Methods: The address history of ALS patients belonging to the population-based Piemonte and Valle d'Aosta registry (PARALS), diagnosed between 2007 and 2014, was obtained for the 20 years prior to the onset date. The smoothed ALS incidence per year (im) was compared with the percentage of area covered by each crop for each municipality. A proximity score was calculated for each cropland by geolocation, measuring the percentage of area surrounding patients’ residence for variable radii, and was used to compare croplands exposure and phenotype. Results: We observed an increased ALS incidence in the municipalities with a higher percentage of area covered by arable crops (R = 0.191, p < 0.001). Age at onset was significantly lower in those patients who lived near arable crops, with a median anticipation ranging from 1.8 to 3.4 years; using historical data, a significant anticipation was found also for patients living near vineyards. Discussion: Our study proved a direct association between arable crops and ALS risk and an inverse association between arable crops and vineyards proximity and age at onset, suggesting the possible causative role of specific environmental contaminants.