Risk factors in Swedish young men for amyotrophic lateral sclerosis in adulthood

Maria Åberg,Kjell Torén,Linus Schiöler,Hans Nissbrandt,Margda Waern,Jenny Nyberg,Josefina Robertson,Georg Kuhn

doi:10.1007/s00415-017-8719-1

Abstract

Recent research suggests that the incidence of amyotrophic lateral sclerosis (ALS) may be on the rise. Since ALS becomes predominant in later life, most studies on causal factors are conducted in middle-aged or older populations where potentially important influences from early life can usually not be adequately captured. We aimed to investigate predictors in young Swedish men for ALS in adulthood. Therefore, we performed a prospective cohort study of young men (aged 16–25, n = 1,819,817) who enlisted 1968–2005 and took part in comprehensive conscription examinations. Incident cases of ALS (n = 526) during up to 46 years of follow-up were identified in the National Hospital Register and Swedish Cause of Death Register. Those who developed ALS had lower BMI (body mass index) at conscription than their peers (p = 0.03). The risk of ALS during follow-up was calculated with Cox proportional hazards models. No associations were found with physical fitness, erythrocyte sedimentation rate, or non-psychotic mental disorders. Low overall muscle strength compared to high overall muscle strength [hazard ratio (HR) 1.36; 95% confidence interval (CI) 1.01–1.83] and low BMI (a one-unit increase HR 0.96; 95% CI 0.93–0.99) and lower erythrocyte volume fraction (a one-unit increase HR 0.96; 95% CI 0.92–0.998) were the statistically significant predictors for ALS in adjusted models. These findings provide novel epidemiologic evidence of a prospective association between low overall muscle strength and erythrocyte volume fraction in young men and ALS risk.

Highlights

Among the rare adult-onset motor neuron diseases, amyotrophic lateral sclerosis (ALS) is the most common
Low BMI, and lower erythrocyte volume fraction in young men were associated with increased risk of ALS in this large male cohort
ALS amyotrophic lateral sclerosis, BMI body mass index, Wmax maximal workload; NS non-significant, mm millimeter, h hour, kg kilogram, N newton, SD standard deviation a p values were adjusted for calendar year b Performance was trichotomized as low, medium, and high c Performance was trichotomized as low, medium, and high d Before/at conscription parental education, erythrocyte sedimentation rate, or psychiatric disorders

Summary

Introduction

Among the rare adult-onset motor neuron diseases, amyotrophic lateral sclerosis (ALS) is the most common. It is typically fatal within 2–5 years of symptom onset [1]. Patients with early onset ALS commonly demonstrate a relatively longer survival [2]. The incidence of ALS is largely uniform across most parts of the world, but an increasing ALS incidence in recent years has been demonstrated both internationally [3] and in Sweden [4]. The epidemiological evidence of associations with ALS is inconsistent [12,13,14,15].

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