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

Eilis J. O'Reilly*, Molin Wang, Hans-Olov Adami, Alvaro Alonso, Leslie Bernstein, Piet van den Brandt, Julie Buring, Sarah Daugherty, Dennis Deapen, D. Michal Freedman, Dallas R. English, Graham G. Giles, Niclas Hakansson, Tobias Kurth, Catherine Schairer, Elisabete Weiderpass, Alicja Wolk, Stephanie A. Smith-Warner

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.
Original languageEnglish
Pages (from-to)396-406
Number of pages11
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Issue number5-6
Publication statusPublished - 1 Jan 2018


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


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