High BMI is associated with low ALS risk A population-based study

Objective To investigate the temporal relationship among prediagnostic body mass index (BMI), weight change, and risk of amyotrophic lateral sclerosis (ALS). Methods From the compulsory Norwegian tuberculosis screening program, we collected objectively measured BMI from 85% of all citizens (near 1.5 million) between 20 and 70 years of age living in 18 of 19 Norwegian counties between 1963 and 1975. For those who participated in later health surveys, we collected further information on weight change, lifestyle, and health. We identified ALS cases until September 2017 through national registries of diagnoses at death and at encounters with the specialist health service. Both Cox hazard models and flexible parametric survival models were fitted to address our research question. Results We identified 2,968 ALS cases during a mean of 33 (maximum 54) years follow-up. High prediagnostic BMI was associated with low subsequent ALS risk across the typical ALS ages in both sexes. Overall, hazard ratio (HR) for ALS per 5-unit increase in prediagnostic BMI was 0.83 (95% confidence interval [CI] 0.79-0.88). After an initial increase during the first 10 years, it decreased almost linearly throughout the observation period and was 0.69 (95% CI 0.62-0.77) after 50 years. Those in the quartile with highest weight gain had lower ALS risk than those in the lowest quartile (HR 0.63, 95% CI 0.44-0.89). Conclusion High BMI and weight gain are associated with low ALS risk several decades later. The strength of the association between BMI and ALS risk increases up to 50 years after BMI measurement.