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Abstract
Our objective was to determine if amyotrophic lateral sclerosis (ALS) risk varies according to body mass index (BMI) captured up to three decades earlier. At baseline 537,968 females and 562,942 males in five ongoing cohorts reported height, current weight and weight at age 18/21 years. During 14–28 years of follow-up, 1153 participants developed ALS. Cohort-specific Cox proportional hazards models were used to estimate rates that were then pooled with random-effects models. Results showed that lower BMI at baseline was associated with ALS; for each 5-unit increase in BMI, ALS rates were 21% lower (95% CI 14% 27%). Compared to individuals with healthy BMI, ALS rates were significantly lower among the overweight (RR = 0.76 (95% CI 0.62–0.93)) and obese (RR = 0.73 (95% CI 0.55–0.96)). Among never smokers the association persisted: RR = 0.75 (95% CI 0.65–0.85) for each 5-unit increase. Excluding the first seven years of follow-up, the associations were materially unchanged suggesting that weight loss from undiagnosed disease does not fully explain the findings. Overall, 75% of males and females had a healthy BMI at age 18/21 years, 15% of males and 8% of females were overweight or obese; there was no association with ALS although numbers with an unhealthy weight were small. In conclusion, these findings support an association between lower premorbid BMI and ALS.
Declaration of interest: The authors have not completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest at this time. The authors alone are responsible for the content and writing of the paper. This work was supported by a grant from the NIH/National Institute of Neurological Diseases and Stroke. Nurses’ Health Study is funded by a NIH program project and Health Professional Follow-up Study also by a NIH program project. The funding agencies had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.