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Research paper
Multicentre, cross-cultural, population-based, case–control study of physical activity as risk factor for amyotrophic lateral sclerosis
  1. Anne E Visser1,
  2. James P K Rooney2,
  3. Fabrizio D’Ovidio3,
  4. Henk-Jan Westeneng1,
  5. Roel C H Vermeulen4,
  6. Ettore Beghi5,
  7. Adriano Chiò3,
  8. Giancarlo Logroscino6,7,
  9. Orla Hardiman2,
  10. Jan H Veldink1,
  11. Leonard H van den Berg1
  12. for the Euro-MOTOR consortium
    1. 1 Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands
    2. 2 Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland
    3. 3 “Rita Levi Montalcini” Department of Neuroscience, University of Torino, Turin, Italy
    4. 4 Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands
    5. 5 Department of Neuroscience, IRCCS – Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy
    6. 6 Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari "Aldo Moro", Pia Fondazione Cardinale G. Panico, Lecce, Italy
    7. 7 Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari, Italy
    1. Correspondence to Professor Leonard H van den Berg, Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht 3508 GA, The Netherlands; L.H.vandenBerg{at}umcutrecht.nl

    Abstract

    Objective To investigate the association between physical activity (PA) and amyotrophic lateral sclerosis (ALS) in population-based case–control studies in three European countries using a validated and harmonised questionnaire.

    Methods Patients with incident ALS and controls were recruited from five population-based registers in The Netherlands, Ireland and Italy. Demographic and data regarding educational level, smoking, alcohol habits and lifetime PA levels in both leisure and work time were gathered by questionnaire, and quantified using metabolic equivalent of task scores. Logistic regression models adjusting for PA-related factors were used to determine the association between PA and ALS risk, and forest plots were used to visualise heterogeneity between regions.

    Results 1557 patients and 2922 controls were included. We found a linear association between ALS and PA in leisure time (OR 1.07, P=0.01) and occupational activities (OR 1.06, P<0.001), and all activities combined (OR 1.06, P<0.001), with some heterogeneity between regions: the most evident association was seen in the Irish and Italian cohorts. After adjustment for other occupational exposures or exclusion of patients with a C9orf72 mutation, the ORs remained similar.

    Conclusion We provide new class I evidence for a positive association between PA and risk of ALS in a large multicentre study using harmonised methodology to objectively quantify PA levels, with some suggestions for population differences.

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    Footnotes

    • JHV and LHB contributed equally.

    • AEV, JPKR and FD’O contributed equally.

    • Contributors AEV: study concept and design, data collection and processing, statistical analyses, contribution to the analysis and interpretation of data and writing of the manuscript. JPKR and FD: study concept and design, data collection and processing, statistical analyses, contribution to the analysis and interpretation of data, revision of the manuscript for important intellectual content. HJW: study concept and design, statistical analyses, contribution to the analysis and interpretation of data, revision of the manuscript for important intellectual content. RCHV: study concept and design, contribution to the analysis and interpretation of data, revision of the manuscript for important intellectual content and provided study supervision. EB, AC, GL, OH, JHV and LHvdB: study concept and design, data collection and processing, contribution to the analysis and interpretation of data, revision of the manuscript for important intellectual content, provided study supervision and obtained funding.

    • Funding The research leading to these results has received funding from the European community’s health seventh framework programme (FP7/2007–2013; grant agreements no. 259867), The Netherlands ALS foundation and The Netherlands Organisation for Health Research and Development (Vici Scheme, JPND (STRENGTH)).

    • Competing interests AEV, FD, HJW, RCHV and GL report no disclosures. JPKR reports grants from health research board, during the conduct of the study. EB reports grants from UCB-Pharma, grants from Shire, grants from EISAI, personal fees from Viropharma, grants from Italian Ministry of Health, grants from European Union, grants from Fondazione Borgonovo, grants from Associazione IDIC 15, outside the submitted work. AC reports personal fees from Biogen Idec, personal fees from Cytokinetics, grants from Italfarmaco, personal fees from Mitsubishi, outside the submitted work. OH reports grants from framework 7 EUROMOTOR project, grants from Health Research Board Ireland, grants from Science Foundation Ireland, during the conduct of the study; personal fees from ALS FTD Journal, outside the submitted work. JHV reports other from Vertex Pharmaceuticals, outside the submitted work. LHvdB reports grants from Netherlands ALS Foundation, grants from The Netherlands Organisation for Health Research and Development, during the conduct of the study; grants from Baxalta, grants from Prinses Beatrix Spierfonds, grants from European Community’s Health Seventh Framework Programme, outside the submitted work; LHvdB serves on scientific advisory boards for the Prinses Beatrix Spierfonds, Thierry Latran Foundation, Biogen and Cytokinetics and serves on the editorial board of amyotrophic lateral sclerosis and frontotemporal degeneration and the journal of neurology, neurosurgery and psychiatry.

    • Patient consent Obtained.

    • Ethics approval The relevant institutional review boards gave ethical approval.

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

    • Collaborators SCILLA Working Group collaborators: Andrea Bruno, MD (Department of Nuclear Medicine, Papa Giovanni XXIII Hospital, Bergamo, Italy); Carlo De Fanti, MD, Sara Fascendini, MD, Angela Tomasoni, MD (European Foundation for Biomedical Research, Alzheimer Center of Excellence, Briolini Hospital of Gazzaniga, Bergamo, Italy); Marco Arnaboldi, MD, Manuela Valsecchi, MS (Department of Neurology and Stroke Unit, Sant’Anna Hospital, Como, Italy); Massimo Moleri, MD (Neurology Unit, San Francesco Clinic, Bergamo, Italy); Marco Poloni, MD, Dario Alimonti, MD (Department of Neurology, Papa Giovanni XXIII Hospital, Bergamo, Italy); Fabrizio Tagliavini, MD, Veronica Redaelli, MD, Giuseppe Di Fede, MD, Ilaria Bizzozero, PsyD, Sara Prioni, PsyD (Division of Neurology V/Neuropathology, Scientific Institute for Research, Hospitalization, and Care (IRCCS), Foundation "Carlo Besta" Neurological Institute, Milan, Italy); Euro-MOTORconsortium: Anneke J van der Kooi, MD, PhD (Department of Neurology, Amsterdam Medical Center, University of Amsterdam, Amsterdam, The Netherlands); Joost Raaphorst, MD, PhD (Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands); Andrea Calvo, MD, PhD (“Rita Levi Montalcini” Department of Neuroscience, University of Torino, Torino, Italy); Cristina Moglia, MD, PhD (“Rita Levi Montalcini” Department of Neuroscience, University of Torino, Torino, Italy); Federico Casale, PhD (“Rita Levi Montalcini” Department of Neuroscience, University of Torino, Torino, Italy); Antonio Canosa, MD, PhD (“Rita Levi Montalcini” Department of Neuroscience, University of Torino, Torino, Italy); Umberto Manera, MD (“Rita Levi Montalcini” Department of Neuroscience, University of Torino, Torino, Italy); Davide Bertuzzo, MD (“Rita Levi Montalcini” Department of Neuroscience, University of Torino, Torino, Italy); Letizia Mazzini, MD (ALS Centre, Department of Neurology, "Maggiore della Carità", University Hospital, Novara, Italy); Enrica Bersano, MD (ALS Centre, Department of Neurology, "Maggiore della Carità", University Hospital, Novara, Italy); Mark Heverin (Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland); Alice Vadja, PhD (Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland); Elisabetta Pupillo (Department of Neurosciences, IRCSS, Mario Negri Institute of Pharmacological Research, Milan, Italy); Giancarlo Comi, MD (Nilo Riva MD, IRCCS San Raffaele Hospital, Milan, Italy); Christian Lunetta, MD (NEMO Clinical Center, Serena Onlus Foundation, Niguarda Ca’ Granda Hospital, Milan, Italy); Francesca Gerardi, DrBT (NEMO Clinical Center, Serena Onlus Foundation, Niguarda Ca’ Granda Hospital, Milan, Italy); Massimiliano Filosto, MD (Civil Hospital of Brescia, Brescia, Italy); Maria Sofia Cotelli, MD (Civil Hospital of Brescia, Brescia, Italy); Fabrizio Rinaldi, MD (Civil Hospital of Brescia, Brescia, Italy); Luca Chiveri, MD (Ospedale Valduce, Como, Italy); Maria Cristina Guaita, MD (A.O. Civil Hospital, Legnano, Italy); Patrizia Perrone, MD (A.O. Civil Hospital, Legnano, Italy); Ceroni Mauro, MD (IRCCS National Neurorological Institute “C.Mondino”, Pavia, Italy); Luca Diamanti, MD (IRCCS National Neurorological Institute “C.Mondino”, Pavia, Italy); Carlo Ferrarese, MD (University of Milano-Bicocca, "San Gerardo" Hospital, Monza, Italy); Lucio Tremolizzo, MD (University of Milano-Bicocca, "San Gerardo" Hospital, Monza, Italy); Maria Luisa Delodovici, MD (“Ospedale di Circolo, Fondazione Macchi”, Varese, Italy); Giorgio Bono, MD (“Ospedale di Circolo, Fondazione Macchi”, Varese, Italy); Chiara Zecca, DrBiol (Department of Clinical Research in Neurology, University of Bari "A. Moro" at Pia Fondazione "Card. G. Panico", Tricase, Italy); Rosanna Tortelli, MD (Department of Clinical Research in Neurology, University of Bari "A. Moro" at Pia Fondazione "Card. G. Panico", Tricase, Italy).

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