Abstract
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor neuron with very few known risk factors. We conducted a spatial epidemiologic analysis of ALS incidence in Denmark to assess the contribution of sociodemographic determinants to geographic variation. METHODS: We analyzed 4249 ALS cases (1982-2013), each with 100 controls matched on sex and birth year. Odds ratio and 95% confidence bands at birth and diagnosis/index locations were calculated using generalized additive models. We included a bivariate spatial smooth for location in our conditional logistic regression adjusted for socioeconomic status and marital status. We also conducted analyses adjusted for both birth and diagnosis addresses to separate location effects. RESULTS: We observed significantly elevated ALS odds near Copenhagen for both the birth and diagnosis period analyses. Sociodemographic factors did not explain the observed patterns. When we further adjusted our spatial analyses by including both birth and diagnosis addresses, the significant area of elevated male ALS odds by birth address shifted to northwest Denmark away from Copenhagen, and there was little evidence of variation among women. Geographic variation at diagnosis differed between male and females, suggesting that patterns are not just due to regional variation in case ascertainment. CONCLUSION: ALS incidence in Denmark is associated with both location at birth and diagnosis, suggesting that geographic variation may be due to exposures occurring at birth or closer to diagnosis, although the latter could relate to case ascertainment issues.