title: Exploring the fitness hypothesis in ALS: a population-based case-control study of parental cause of death and lifespan.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Visser
authors.affiliation: Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Meinie
authors.initials: M
authors.lastname: Seelen
authors.affiliation: Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hulsbergen
authors.affiliation: Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Joris
authors.initials: J
authors.lastname: de Graaf
authors.affiliation: Department of Neurology, Amsterdam Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.affiliation: Department for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Raaphorst
authors.affiliation: Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.affiliation: Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology; D016022:Case-Control Studies; D002423:Cause of Death; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007899:Leisure Activities; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010290:Parents; D012307:Risk Factors; D011795:Surveys and Questionnaires
keywords: Amyotrophic lateral sclerosis; cardiovascular; case-control studies; epidemiology; fitness; motor neuron disease