Prediagnostic body size and risk of amyotrophic lateral sclerosis death in 10 studies

Objectives and Methods: Using pooled multivariable-adjusted rate ratios (RR), we explored relationships between prediagnostic body-mass-index (BMI), waist-to-hip-ratio (WHR), and weight-gain during adulthood, and ALS in 419,894 women and 148,166 men from 10 community-based cohorts in USA, Europe, and Australia; 428 ALS deaths were documented in women and 204 in men. Results: Higher mid-to-later adulthood BMI was associated with lower ALS mortality. For 5kg/m(2) increased BMI, the rate was 15% lower (95% confidence interval [CI]: 4-24%;p=0.005). Although a clear linear trend was not evident for WHR at enrollment (p=0.099) individuals in the highest cohort-specific quartile had 27% (95%CI: 0-47%; p=0.053) lower ALS compared to those in the lowest. BMI in early adulthood did not predict ALS; fewer than 10% of participants had early adulthood BMI >25kg/m(2), limiting power. Weight-gain during adulthood was strongly associated with lower ALS; for an additional 1kg gain in weight/year, the RR=0.43 (95%CI: 0.28-0.65; p<0.001). Associations persisted when adjusted for diabetes at enrollment, restricted to never-smokers, and ALS deaths in the 5 years after enrollment were excluded (accounting for recent weight loss). Conclusions: These findings confirm somewhat conflicting, underpowered evidence that adiposity is inversely associated with ALS. We newly demonstrate that weight-gain during adulthood is strongly predictive of lower ALS risk.