LAUSR

The clinical onset of amyotrophic lateral sclerosis (ALS) is often reported as abrupt whether the disease is apparently sporadic or inherited. However, the factors initiating the onset of the disease remain obscure, but they are clearly important for understanding the pathogenesis and, certainly, for devising means of modifying the natural history of the disease [1]. A high level of physical fitness and a thin and athletic body habitus have been found to be associated with a higher risk of acquiring ALS [2,3]. However, a recent meta-analysis suggested that physical exercise is not a risk factor, unless exercise is undertaken at high levels [4]. Trauma is probably not a risk factor, unless repeated or severe trauma has occurred [5]. An increased risk for ALS has been reported in the context of a high dietary intake of carbohydrates, glutamate and fat, with a low intake of various micronutrients such as vitamin E, omega-3 polyunsaturated fatty acids, carotenoids and fruits and vegetables [6,7], whereas omega-3 polyunsaturated fats are thought to confer a reduced risk. Smoking is associated with an increased risk of ALS. However, the effect size of these risk factors is not high, and none can be regarded as essential factors triggering the disease onset in a susceptible person. Indeed, the factors contributing to genetic ALS susceptibility are themselves undefined, except in the relatively rare examples of certain mutations, e.g. the C9orf72 mutation. Other putative environmental factors include exposure to environmental toxins such as lead, mercury, organic solvents and insecticides, but the evidence for these factors in the triggering of ALS is controversial [8]. Cardiovascular fitness, determined by the absence of symptomatic coronary artery disease, has been found to be associated with a slightly higher relative risk of ALS, but not for Parkinson’s disease or multiple sclerosis [9]. In this issue of the journal, Longinetti et al [10] report that amongst nearly 2 million young male military recruits to the Swedish Army those with higher IQ values had a higher risk of ALS after age 56 years. Recruits with a higher stress resilience, a concept of potential importance given reports of a higher risk for ALS in the context of psychological stress, had a higher risk of ALS by age 55 years and younger. The rationale underlying these findings is uncertain. In addition, they found that recruits with greater physical fitness had a higher risk of ALS below age 45 years. Individuals with a body mass index equal to or greater than 25 had a lower risk of ALS at any age. The study was based on follow-up using the Swedish Patient Register system that was continued from 1987 to 2013. This work has a number of limitations: only males were studied, older subjects were not studied, and the military induction examination was relatively limited and did not exclude poor motivation in performance of the required tasks. Information on other important factors, e.g. smoking history, post-military exercise history, details about possible trauma, a possible family history of ALS, and the lipid profile, was not sought. However, the study does indicate the importance of studying possible environmental risk factors as triggers for ALS onset.