• Anne E Visser, Meinie Seelen, Alexander Hulsbergen, Joris de Graaf, Anneke J van der Kooi, Joost Raaphorst, Jan H Veldink, and Leonard H van den Berg.
• Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands.
• J. Neurol. Neurosurg. Psychiatr. 2017 Jul 1; 88 (7): 550-556.

ObjectiveTo investigate the theory of premorbid fitness in amyotrophic lateral sclerosis (ALS), we studied whether a common genetic profile for physical or cardiovascular fitness was manifest in progenitors leading to less cardiovascular death and a longer lifespan in parents of patients with ALS compared with parents of controls.MethodsPatient and disease characteristics, levels of physical activity, parental cause and age of death were obtained using a structured questionnaire from a population-based, case-control study of ALS in the Netherlands. Logistic regression was used for the analyses of parental cause of death and levels of physical activity. Cox proportional hazard models were applied to study the association between parental survival and ALS, or specific patient subgroups. All models were adjusted for age at inclusion, level of education, body mass index, diabetes, hypercholesterolaemia and hypertension.Results487 patients and 1092 controls were included. Parents of patients died less frequently from a cardiovascular disease compared with parents of controls (OR=0.78, p=0.009). Their survival, however, was neither significantly longer nor shorter. Neither rates of cardiovascular causes of death, nor survival of parents was related to the extent to which patients were physically active in leisure time (all p>0.05).ConclusionsExploring the fitness hypothesis in the pathogenesis of ALS, our findings provide evidence for a shared mechanism underlying a favourable cardiovascular fitness profile and ALS susceptibility.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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