High pre-diagnostic body mass index (BMI) and weight gain are associated with a lower risk for amyotrophic lateral sclerosis (ALS) several decades later, according to a study published in Neurology.

In this population-based study, researchers collected objectively measured BMI from 85% of citizens aged 20 to 70 years who and living in 18 out of 19 Norwegian counties between 1963 and 1975. A primary cohort (n=1,468,250) was then derived after exclusions such as BMI >60 or <12 kg/m2 and possible tuberculosis. Data collected included anthropometric characteristics, year and month of birth, age, sex, county residence, vaccination status, results of the tuberculosis skin test, and X-ray findings.

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ALS cases were ascertained through the Norwegian Cause of Death Registry and the Norwegian Patient Registry. Each participant contributed follow-up time from the date of tuberculosis screening to the date of ALS death, ALS incidence, death from other causes, emigration, or September 1, 2017 (the end of study follow-up), whichever came first.


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During a mean follow-up time of 33 years (standard deviation [SD] 14), 2968 ALS cases were registered. The hazard ratio (HR) for ALS per each 5-unit increase in BMI at the tuberculosis screening was 0.83 (95% confidence interval [CI], 0.79-0.88), with a difference across BMI categories (P <.001 for trend). Compared to patients with low-normal BMI, both overweight and obese individuals were at lower risk for ALS (HR 0.82; 95% CI, 0.74-0.98 vs HR 0.66; 95% CI, 0.56-0.78, respectively).

The inverse association with ALS risk and BMI substantially weakened during the first years after the measurement. After approximately 15 years, risk increased steadily during the remainder of the 50-year observation period. The HR for ALS per each 5-unit increase in BMI was 0.85 after 25 years (95% CI, 0.80-0.91) and 0.69 after 50 years (95% CI, 0.62-0.77). A sensitivity analysis was conducted to address the possibility of reverse causality for which the first 10 years of follow-up were excluded; results did not change materially.

Limitations of this study included making adjustments for only smoking and physical activity in a relatively young subset of the primary cohort at the time of tuberculosis screening, which may not necessarily be representative of the primary cohort. Additionally, the study population was a homogenous cohort of white citizens, which limits the generalizability of these results.

The researchers suggested that while high BMI is associated with low ALS risk in all typical ALS ages, long follow-up is necessary to assess the relationship between anthropometric measures and ALS risk. These results confirm findings from 2 case-control studies which reported weight loss 5 to 10 years prior to ALS diagnosis, but contradict a previous finding showing higher mid-adulthood BMI is associated with lower ALS mortality. Further research is needed to reveal possible mechanisms and clinical consequences of this finding.

Reference

Nakken O, Meyer HE, Stigum P, Holmøy T. High BMI is associated with low ALS risk [published online June 26, 2019]. Neurology. doi: 10.1212/WNL.0000000000007861