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

Abstract

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 5 kg/m² 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 >25 kg/m², 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.

Keywords:

• Amyotrophic lateral sclerosis
• body mass index
• waist-to-hip ratio
• weight gain

Declaration of interest

There are no other conflicts to report.

This work was supported by NIH grant [R01-NS072494-01A1] awarded to EOR and NCI grant [CA55075] awarded to SSW. The COSM and SMC cohorts are supported by the Swedish Research Council and by Strategic funds at Karolinska Institutet, Stockholm, Sweden. TK has received within the last 2 years investigator-initiated research funding from the French National Research Agency, the US National Institutes of Health, and the Parkinson’s Research Foundation. Further, he has received honoraria from the American Academy of Neurology and Allergan for educational lectures and from the BMJ and Cephalalgia for editorial services.

Additional information

Funding

This work was supported by NIH grant [R01-NS072494-01A1] awarded to EOR and NCI grant [CA55075] awarded to SSW. The COSM and SMC cohorts are supported by the Swedish Research Council and by Strategic funds at Karolinska Institutet, Stockholm, Sweden. TK has received within the last 2 years investigator-initiated research funding from the French National Research Agency, the US National Institutes of Health, and the Parkinson’s Research Foundation. Further, he has received honoraria from the American Academy of Neurology and Allergan for educational lectures and from the BMJ and Cephalalgia for editorial services.