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Amyotroph Lateral Scler Frontotemporal Degener. 2018 Aug;19(5-6):396-406. doi: 10.1080/21678421.2018.1452944. Epub 2018 Apr 16.

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

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a Department of Nutrition , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
b School of Public Health, College of Medicine , University College Cork , Cork , Ireland.
c Channing Division of Network Medicine , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.
d Department of Epidemiology , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
e Department of Medical Epidemiology and Biostatistics , Karolinska Institutet , Stockholm , Sweden.
f Department of Epidemiology , Rollins School of Public Health, Emory University , Atlanta , GA , USA.
g Division of Cancer Etiology, Department of Population Science , Beckman Research Institute and City of Hope National Medical Center , Duarte , CA , USA.
h Department of Epidemiology, School for Oncology and Developmental Biology (GROW) , Maastricht University , Maastricht , The Netherlands.
i Division of Preventive Medicine , Brigham and Women's Hospital, Harvard Medical School , Boston , MA , USA.
j CER Methods & Infrastructure , Patient-Centered Outcomes Research Institute , Washington, DC , USA.
k Division of Cancer Epidemiology and Genetics , National Cancer Institute , Rockville , MD , USA.
l Cancer Epidemiology Centre, Cancer Council of Victoria , Melbourne , Australia.
m Centre for Epidemiology and Biostatistics , Melbourne School of Population and Global Health, The University of Melbourne , Melbourne , Australia.
n Division of Nutritional Epidemiology , National Institute of Environmental Medicine, Karolinska Institutet , Stockholm , Sweden.
o Institute of Public Health , Charité - Universitätsmedizin Berlin , Germany.
p Department of Community Medicine, Faculty of Health Sciences , University of Tromsø, The Arctic University of Norway , Tromsø , Norway.
q Department of Research , Cancer Registry of Norway , Oslo , Norway , and.
r Genetic Epidemiology Group , Folkhälsan Research Center , Helsinki , Finland.



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.


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).


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.


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

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