Incidence of amyotrophic lateral sclerosis in Sardinia, Italy: age-sex interaction and spatial-temporal variability

Objective: This study assessed amyotrophic lateral sclerosis (ALS) incidence in Sardinia, Italy, and the combined contribution of age and gender to disease risk. We also checked disease incidence for spatial-temporal variability. Methods: ALS patients from all neurological centers of the study area who had onset during 2010-2019 and fulfilled El Escorial revised diagnostic criteria were included. Incidence was calculated for the overall study area and each province separately. Additive interaction between age and sex on ALS incidence was assessed. Results: The average crude annual incidence rate was 3.6/100,000 person-years (95% CI, 3.2-4.1), 3.1/100,000 person-years (95% CI, 2.7-3.5) when age-adjusted. Incidence was greater among people aged >= 65 years and men, with the two variables undergoing significant additive interaction. Incidence increased yearly over the study period, with annual incidence correlating with the increasing yearly frequency of people aged >= 65 years, but not with the proportion of incident cases carrying genetic mutations. Stratifying by province, the rates from Oristano and South Sardinia were higher than the rate from Cagliari. ALS patients from areas at different risk were comparable for frequency of clinical/genetic features. Conclusion: ALS incidence in Sardinia was in the upper part of the European range of variability. We also provided new information about age and sex as risk factors for ALS, showing male sex as a modifier of the effect of aging on ALS incidence. Spatial-temporal variations in ALS incidence correlated to changes in the proportion of the aging population rather than to the distribution of genetic factors.