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.

Figure 1:

Pooled results for 5kg/m2 increase in BMI at enrollment. Pooled RR=0.85 (95% CI: 0.76 to 0.95); p=0.005). Among women, pooled RR=0.87 (95% CI: 0.77 to 0.99); p=0.036). Among men, pooled RR=0.75 (95% CI: 0.56 to 1.01); p=0.062)

Figure 2:

BCDDP (w), SMC (w), WHS (w), IWHS (w), MCCS (w & m), WLHS (w) and COSM (m) had waist and hip measurements, however, WLHS was not included in the analyses because of small case numbers. Quartiles are cohort-specific (and gender specific in MCCS), then pooled. All tests of heterogeneity had p-values >0.05. Analyses are adjusted for age, education, race, smoking, and physical activity, Further adjustment for BMI at baseline changed effect sizes minimally.