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Exploring the fitness hypothesis in ALS: a population-based case-control study of parental cause of death and lifespan
  1. Anne E Visser1,
  2. Meinie Seelen1,
  3. Alexander Hulsbergen1,
  4. Joris de Graaf1,
  5. Anneke J van der Kooi2,
  6. Joost Raaphorst3,
  7. Jan H Veldink1,
  8. Leonard H van den Berg1
  1. 1 Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands
  2. 2 Department of Neurology, Amsterdam Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  3. 3 Department for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  1. Correspondence to Dr Leonard H van den Berg, Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands; l.h.vandenberg{at}


Objective To 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.

Methods Patient 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.

Results 487 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).

Conclusions Exploring 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.

  • Amyotrophic lateral sclerosis
  • case-control studies
  • epidemiology
  • cardiovascular
  • fitness
  • motor neuron disease

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  • Funding This work was supported by the Netherlands ALS Foundation. LHvdB received a grant from the Netherlands Organisation for Health Research and Development (Vici scheme).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Presentation statement LH vdB serves on scientific advisory boards for the Prinses Beatrix Spierfonds, Thierry Latran Foundation, Biogen and Cytokinetics; received an educational grant from Baxalta; serves on the editorial board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration and the Journal of Neurology, Neurosurgery and Psychiatry and receives research support from the Prinses Beatrix Spierfonds, Netherlands ALS Foundation, the European Community's Health Seventh Framework Programme (grant agreement no 259867), The Netherlands Organisation for Health Research and Development (Vici Scheme, JPND (SOPHIA, STRENGTH, ALSCare)).

  • Presentation statement JHV and LHvdB contributed equally.

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