Premorbid body mass index and risk of amyotrophic lateral sclerosis

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.

Figure. Pooled Relative Risks (95% Confidence Intervals) of Amyotrophic Lateral Sclerosis by Body Mass Index Among Never Smokers

Study-specific and pooled multivariable relative risk and 95% confidence interval of amyotrophic lateral sclerosis for a 5 unit increase in BMI among never smokers (375 cases). The squares and horizontal lines correspond to the study-specific multivariable relative risk (RR) and 95% confidence interval (CI), respectively. The area of the squares reflects the study weight (inverse of the variance). The diamond represents the pooled multivariable RR and 95% CI. Pooled RR =0.75 (95% CI: 0.65-0.85; p<0.0001); p for heterogeneity =0.83. Among never smokers, with a BMI of 18.5-<23 as the reference category the RRs (95% CI) were 2.74 (1.39, 5.41) for BMI <18.5; 0.85 (0.63-1.14) for BMI 23-<25; 0.71 (0.53-0.96) for BMI 25-<27.5; 0.69 (0.48-1.00) for a BMI 27.5-<30; and 0.59 (0.41-0.86) for BMI of 30+