Life Course of Physical Activity and Risk and Prognosis of Amyotrophic Lateral Sclerosis in a German ALS Registry
Angela Rosenbohm, Raphael Peter, Johannes Dorst, Jan Kassubek, Dietrich Rothenbacher, Gabriele Nagel, Albert C. Ludolph, on behalf of the ALS Registry Swabia Study Group, Frank Andres, Guy Arnold, Hartmut Baier, Hansjoerg Baezner, James Beattie, Friedrich Behne, Dietmar Bengel, Axel Boertlein, Bracknies Vera, Burkhard Alber, Mathias Buttmann, Silke Dempewolf, Christian Dettmers, Wolfgang Freund, Thomas Gasser, Hans-Juergen Gold, Gerhard Hamann, Martin Hecht, Bernhard Heimbach, Birgit Herting, Roman Huber, Paul-Juergen Huelser, Karlheinz HuberHartmann, Eric Jüttler, Attila Kaspar, Rolf Kern, Hubert Kimmig, Klötzsch Christof, Anastasios Chatzikonstantinou, Thomas Klopstock, Andreas Kohler, Christoph Lichy, Alfred Lindner, Paul Lingor, Dorothee Lulé, Jens Metrikat, Oliver Meudt, Andreas Meyer, Andrea Naegele, Markus Naumann, Klaus-Dieter Neher, Oliver Neuhaus, Clemens Neusch, Ludwig Niehaus, Jan Raape, Peter Ratzka, Matthias Reinhard, Johann Rothmeier, Michael Sabolek, Martin Schabet, MDMario SchaeffVogelsang, Caroline Schell, Caroline Schell, Barbara Schweigert, Norbert Sommer, Mark Stroick, Mathis Synofzik, Hayrettin Tumani, Jens Volkmann, Markus Weiler, Wolfgang Wick, Christian Opherk, Cornelius Weiller, Daniel Zeller, Jessica Baumgärtner, Christoph Born, Martin Bürgy, Bernhard Connemann, Elmar Etzersdorfer, Hubertus Friederich, Maximilian Gahr, Alex Gogolkiewicz, Ralf Greber, Jochen Gebhardt, Heinz Grunze, Karsten Henkel, Walter Hewer, Andreas Raether, Andreas Joos, Matthias Köhler, Ralf Kozian, Christoph Laske, Alexandros Michaelides, Matthias Munk, Andreas Niestroj, Max Schmauss, Max Schmauss, Katrin SchoenebergerStroick, Kai-Uwe Schoerner, Stefan Spannhorst, Raimund Steber, Christine Thomas
Abstract
BACKGROUND AND OBJECTIVES: Whether physical activity (PA) is a risk factor for amyotrophic lateral sclerosis (ALS) is controversial because data on lifelong PA are rare. The main objective of this study is to provide insight into PA as a potential risk factor for ALS, reporting data on cumulative PA, leisure-time PA, and occupational PA. This study also aims to gather evidence on the role of PA as a prognostic factor in disease course. METHODS: Lifetime PA values collected by questionnaires addressing work and leisure time were quantified into metabolic equivalents (METs). A population-based case-control study embedded in the ALS Registry Swabia served to calculate the odds ratio (OR) of ALS by PA in different time intervals and prognosis. RESULTS: In ALS cases (393 cases, 791 age- and sex-matched controls), we observed reduced total PA at interview and up to 5 years before interview compared to controls. Total PA was not associated with ALS risk 5 to 55 years before interview. Heavy occupational work intensity was associated with increased ALS risk (OR 1.97, 95% confidence interval 1.34, 2.89). Total PA levels were associated with survival in a nonlinear manner: inactive patients and highest activity levels (25 MET-h/wk) revealed the worst survival time of 15.4 and 19.3 months, respectively. Best median survival with 29.8 months was seen at 10.5 MET-h/wk after adjustment for other prognostic factors. DISCUSSION: Lifetime combined PA decreased sharply several years before disease onset compared to controls. The risk of developing ALS was not associated with former total PA levels 5 to 55 years before interview in contrast to occupational PA, probably reflecting work-associated exposures. We found a strong nonlinear association of current and prediagnostic PA level and survival in ALS cases with the best survival with moderate PA. PA intensity may be a disease-modifying factor with an unfavorable outcome in sedentary and hyperactive behavior. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that PA was not associated with the development of ALS.