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Original research
Understanding the relationship between cognitive performance and function in daily life after traumatic brain injury
  1. Lindsay Wilson1,
  2. Lindsay Horton1,
  3. Kevin Kunzmann2,
  4. Barbara J Sahakian3,
  5. Virginia FJ Newcombe4,
  6. Emmanuel A Stamatakis4,
  7. Nicole von Steinbuechel5,
  8. Katrin Cunitz5,
  9. Amra Covic5,
  10. Andrew Maas6,
  11. Dominique Van Praag7,
  12. David Menon4
  13. The CENTER-TBI participants and investigators
    1. 1Division of Psychology, University of Stirling, Stirling, UK
    2. 2MRC Biostatistics Unit, University of Cambridge, Cambridge, UK
    3. 3Department of Psychiatry, University of Cambridge, Cambridge, UK
    4. 4Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
    5. 5Institute of Medical Psychology and Medical Sociology, University Medical Center Goettingen and Georg-August-University, Goettingen, Germany
    6. 6Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium
    7. 7Department of Psychology, Antwerp University Hospital and University of Antwerp, Edegem, Belgium
    1. Correspondence to Professor Lindsay Wilson, Division of Psychology, University of Stirling, Stirling FK9 4LA, UK; l.wilson{at}stir.ac.uk

    Abstract

    Objective Cognitive impairment is a key cause of disability after traumatic brain injury (TBI) but relationships with overall functioning in daily life are often modest. The aim is to examine cognition at different levels of function and identify domains associated with disability.

    Methods 1554 patients with mild-to-severe TBI were assessed at 6 months post injury on the Glasgow Outcome Scale—Extended (GOSE), the Short Form-12v2 and a battery of cognitive tests. Outcomes across GOSE categories were compared using analysis of covariance adjusting for age, sex and education.

    Results Overall effect sizes were small to medium, and greatest for tests involving processing speed (ηp2 0.057–0.067) and learning and memory (ηp2 0.048–0.052). Deficits in cognitive performance were particularly evident in patients who were dependent (GOSE 3 or 4) or who were unable to participate in one or more major life activities (GOSE 5). At higher levels of function (GOSE 6–8), cognitive performance was surprisingly similar across categories. There were decreases in performance even in patients reporting complete recovery without significant symptoms. Medium to large effect sizes were present for summary measures of cognition (ηp2 0.111), mental health (ηp2 0.131) and physical health (ηp2 0.252).

    Conclusions This large-scale study provides novel insights into cognitive performance at different levels of disability and highlights the importance of processing speed in function in daily life. At upper levels of outcome, any influence of cognition on overall function is markedly attenuated and differences in mental health are salient.

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    Footnotes

    • Twitter @vfjn2, @estamatakis

    • Collaborators Cecilia Åkerlund (Department of Physiology and Pharmacology, Section of Perioperative Medicine and Intensive Care, Karolinska Institutet, Stockholm, Sweden), Krisztina Amrein (János Szentágothai Research Centre, University of Pécs, Pécs, Hungary), Nada Andelic (Division of Surgery and Clinical Neuroscience, Department of Physical Medicine and Rehabilitation, Oslo University Hospital and University of Oslo, Oslo, Norway), Lasse Andreassen (Department of Neurosurgery, University Hospital Northern Norway, Tromso, Norway), Audny Anke (Department of Physical Medicine and Rehabilitation, University Hospital Northern Norway, Tromso, Norway), Anna Antoni (Trauma Surgery, Medical University Vienna, Vienna, Austria), Gérard Audibert (Department of Anesthesiology & Intensive Care, University Hospital Nancy, Nancy, France), Philippe Azouvi (Raymond Poincare hospital, Assistance Publique – Hopitaux de Paris, Paris, France), Maria Luisa Azzolini (Department of Anesthesiology & Intensive Care, S Raffaele University Hospital, Milan, Italy), Ronald Bartels (Department of Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands), Pál Barzó (Department of Neurosurgery, University of Szeged, Szeged, Hungary), Romuald Beauvais (International Projects Management, ARTTIC, Munchen, Germany), Ronny Beer (Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria), Bo-Michael Bellander (Department of Neurosurgery & Anesthesia & intensive care medicine, Karolinska University Hospital, Stockholm, Sweden), Antonio Belli (NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham, UK), Habib Benali (Anesthesie-Réanimation, Assistance Publique – Hopitaux de Paris, Paris, France), Maurizio Berardino (Department of Anesthesia & ICU, AOU Città della Salute e della Scienza di Torino - Orthopedic and Trauma Center, Torino, Italy), Luigi Beretta (Department of Anesthesiology & Intensive Care, S Raffaele University Hospital, Milan, Italy), Morten Blaabjerg (Department of Neurology, Odense University Hospital, Odense, Denmark), Peter Bragge (BehaviourWorks Australia, Monash Sustainability Institute, Monash University, Victoria, Australia), Alexandra Brazinova (Department of Public Health, Faculty of Health Sciences and Social Work, Trnava University, Trnava, Slovakia), Vibeke Brinck (Quesgen Systems Inc., Burlingame, California, USA), Joanne Brooker (Australian & New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia), Camilla Brorsson (Department of Surgery and Perioperative Science, Umeå University, Umeå, Sweden), Andras Buki (Department of Neurosurgery, Medical School, University of Pécs, Hungary and Neurotrauma Research Group, János Szentágothai Research Centre, University of Pécs, Hungary), Monika Bullinger (Department of Medical Psychology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany), Manuel Cabeleira (Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Alessio Caccioppola (Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy), Emiliana Calappi (Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy), Maria Rosa Calvi (Department of Anesthesiology & Intensive Care, S Raffaele University Hospital, Milan, Italy), Peter Cameron (ANZIC Research Centre, Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Victoria, Australia), Guillermo Carbayo Lozano (Department of Neurosurgery, Hospital of Cruces, Bilbao, Spain), Marco Carbonara (Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy), Simona Cavallo (Department of Anesthesia & ICU, AOU Città della Salute e della Scienza di Torino - Orthopedic and Trauma Center, Torino, Italy), Giorgio Chevallard (NeuroIntensive Care, Niguarda Hospital, Milan, Italy), Arturo Chieregato (NeuroIntensive Care, Niguarda Hospital, Milan, Italy), Giuseppe Citerio (School of Medicine and Surgery, Università Milano Bicocca, Milano, Italy; NeuroIntensive Care, ASST di Monza, Monza, Italy), Iris Ceyisakar (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Hans Clusmann (Department of Neurosurgery, Medical Faculty RWTH Aachen University, Aachen, Germany), Mark Coburn (Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany), Jonathan Coles (Department of Anesthesia & Neurointensive Care, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK), Jamie D Cooper (School of Public Health & PM, Monash University and The Alfred Hospital, Melbourne, Victoria, Australia), Marta Correia (Radiology/MRI department, MRC Cognition and Brain Sciences Unit, Cambridge, UK), Amra Čović (Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany), Nicola Curry (Oxford University Hospitals NHS Trust, Oxford, UK), Endre Czeiter (Department of Neurosurgery, Medical School, University of Pécs, Hungary and Neurotrauma Research Group, János Szentágothai Research Centre, University of Pécs, Hungary), Marek Czosnyka (Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Claire Dahyot-Fizelier (Intensive Care Unit, CHU Poitiers, Potiers, France), Paul Dark (University of Manchester NIHR Biomedical Research Centre, Critical Care Directorate, Salford Royal Hospital NHS Foundation Trust, Salford, UK), Helen Dawes (Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK), Véronique De Keyser (Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium), Vincent Degos (Anesthesie-Réanimation, Assistance Publique – Hopitaux de Paris, Paris, France), Francesco Della Corte (Department of Anesthesia & Intensive Care, Maggiore Della Carità Hospital, Novara, Italy), Hugo den Boogert (Department of Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands), Bart Depreitere (Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium), Đula Đilvesi (Department of Neurosurgery, Clinical centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia), Abhishek Dixit (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Emma Donoghue (Australian & New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia), Jens Dreier (Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany), Guy-Loup Dulière (Intensive Care Unit, CHR Citadelle, Liège, Belgium), Ari Ercole (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Patrick Esser (Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK), Erzsébet Ezer (Department of Anaesthesiology and Intensive Therapy, University of Pécs, Pécs, Hungary), Martin Fabricius (Departments of Neurology, Clinical Neurophysiology and Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark), Valery L Feigin (National Institute for Stroke and Applied Neurosciences, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland, New Zealand), Kelly Foks (Department of Neurology, Erasmus MC, Rotterdam, the Netherlands), Shirin Frisvold (Department of Anesthesiology and Intensive care, University Hospital Northern Norway, Tromso, Norway), Alex Furmanov (Department of Neurosurgery, Hadassah-hebrew University Medical center, Jerusalem, Israel), Pablo Gagliardo (Fundación Instituto Valenciano de Neurorrehabilitación (FIVAN), Valencia, Spain), Damien Galanaud (Anesthesie-Réanimation, Assistance Publique – Hopitaux de Paris, Paris, France), Dashiell Gantner (ANZIC Research Centre, Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Victoria, Australia), Guoyi Gao (Department of Neurosurgery, Shanghai Renji hospital, Shanghai Jiaotong University/school of medicine, Shanghai, China), Pradeep George (Karolinska Institutet, INCF International Neuroinformatics Coordinating Facility, Stockholm, Sweden), Alexandre Ghuysen (Emergency Department, CHU, Liège, Belgium), Lelde Giga (Neurosurgery clinic, Pauls Stradins Clinical University Hospital, Riga, Latvia), Ben Glocker (Department of Computing, Imperial College London, London, UK), Jagoš Golubovic (Department of Neurosurgery, Clinical centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia), Pedro A Gomez (Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Spain), Johannes Gratz (Department of Anesthesia, Critical Care and Pain Medicine, Medical University of Vienna, Austria), Benjamin Gravesteijn (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Francesca Grossi (5 Department of Anesthesia & Intensive Care, Maggiore Della Carità Hospital, Novara, Italy), Russell L Gruen (College of Health and Medicine, Australian National University, Canberra, Australia), Deepak Gupta (Department of Neurosurgery, Neurosciences Centre & JPN Apex trauma centre, All India Institute of Medical Sciences, New Delhi-110029, India), Juanita A Haagsma (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Iain Haitsma (Department of Neurosurgery, Erasmus MC, Rotterdam, the Netherlands), Raimund Helbok (Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria), Eirik Helseth (Department of Neurosurgery, Oslo University Hospital, Oslo, Norway), Lindsay Horton (Division of Psychology, University of Stirling, Stirling, UK), Jilske Huijben (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Peter J Hutchinson (Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital & University of Cambridge, Cambridge, UK), Bram Jacobs (Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands), Stefan Jankowski (Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK), Mike Jarrett (Quesgen Systems Inc., Burlingame, California, USA), Ji-yao Jiang (Department of Neurosurgery, Shanghai Renji hospital, Shanghai Jiaotong University/school of medicine, Shanghai, China), Faye Johnson (Salford Royal Hospital NHS Foundation Trust Acute Research Delivery Team, Salford, UK), Kelly Jones (National Institute for Stroke and Applied Neurosciences, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland, New Zealand), Mladen Karan (Department of Neurosurgery, Clinical centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia), Angelos G Kolias (Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital & University of Cambridge, Cambridge, UK), Erwin Kompanje (Department of Intensive Care and Department of Ethics and Philosophy of Medicine, Erasmus Medical Center, Rotterdam, The Netherlands), Daniel Kondziella (Departments of Neurology, Clinical Neurophysiology and Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark), Evgenios Koraropoulos (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Lars-Owe Koskinen (Department of Clinical Neuroscience, Neurosurgery, Umeå University, Umeå, Sweden), Noémi Kovács (6 Hungarian Brain Research Program - Grant No. KTIA_13_NAP-A-II/8, University of Pécs, Pécs, Hungary), Ana Kowark (Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany), Alfonso Lagares (Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Spain), Linda Lanyon (Karolinska Institutet, INCF International Neuroinformatics Coordinating Facility, Stockholm, Sweden), Steven Laureys (Cyclotron Research Center, University of Liège, Liège, Belgium), Fiona Lecky (Centre for Urgent and Emergency Care Research (CURE), Health Services Research Section, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK; Emergency Department, Salford Royal Hospital, Salford UK), Didier Ledoux (Cyclotron Research Center, University of Liège, Liège, Belgium), Rolf Lefering (Institute of Research in Operative Medicine (IFOM), Witten/Herdecke University, Cologne, Germany), Valerie Legrand (VP Global Project Management CNS, ICON, Paris, France), Aurelie Lejeune (Department of Anesthesiology-Intensive Care, Lille University Hospital, Lille, France), Leon Levi (Department of Neurosurgery, Rambam Medical Center, Haifa, Israel), Roger Lightfoot (Department of Anesthesiology & Intensive Care, University Hospitals Southhampton NHS Trust, Southhampton, UK), Hester Lingsma (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Andrew I R Maas (Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium), Ana M Castaño-León (Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Spain), Marc Maegele (Cologne-Merheim Medical Center (CMMC), Department of Traumatology, Orthopedic Surgery and Sportmedicine, Witten/Herdecke University, Cologne, Germany), Marek Majdan (Department of Public Health, Faculty of Health Sciences and Social Work, Trnava University, Trnava, Slovakia), Alex Manara (Intensive Care Unit, Southmead Hospital, Bristol, Bristol, UK), Geoffrey Manley (Department of Neurological Surgery, University of California, San Francisco, California, USA), Costanza Martino (Department of Anesthesia & Intensive Care, M. Bufalini Hospital, Cesena, Italy), Hugues Maréchal (Intensive Care Unit, CHR Citadelle, Liège, Belgium), Julia Mattern (Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany), Catherine McMahon (Department of Neurosurgery, The Walton centre NHS Foundation Trust, Liverpool, UK), Béla Melegh (Department of Medical Genetics, University of Pécs, Pécs, Hungary), David Menon (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Tomas Menovsky (Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium), Ana Mikolic (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Benoit Misset (Cyclotron Research Center, University of Liège, Liège, Belgium), Visakh Muraleedharan (Karolinska Institutet, INCF International Neuroinformatics Coordinating Facility, Stockholm, Sweden), Lynnette Murray (ANZIC Research Centre, Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Victoria, Australia), Ancuta Negru (Department of Neurosurgery, Emergency County Hospital Timisoara, Timisoara, Romania), David Nelson (Department of Physiology and Pharmacology, Section of Perioperative Medicine and Intensive Care, Karolinska Institutet, Stockholm, Sweden), Virginia Newcombe (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Daan Nieboer (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), József Nyirádi (János Szentágothai Research Centre, University of Pécs, Pécs, Hungary), Otesile Olubukola (Centre for Urgent and Emergency Care Research (CURE), Health Services Research Section, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK), Matej Oresic (School of Medical Sciences, Örebro University, Örebro, Sweden), Fabrizio Ortolano (Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy), Aarno Palotie (Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Analytic and Translational Genetics Unit, Department of Medicine; Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA), Paul M Parizel (Department of Radiology, University of Antwerp, Edegem, Belgium), Jean-François Payen (Department of Anesthesiology & Intensive Care, University Hospital of Grenoble, Grenoble, France), Natascha Perera (International Projects Management, ARTTIC, Munchen, Germany), Vincent Perlbarg (Anesthesie-Réanimation, Assistance Publique – Hopitaux de Paris, Paris, France), Paolo Persona (Department of Anesthesia & Intensive Care, Azienda Ospedaliera Università di Padova, Padova, Italy), Wilco Peul (Dept. of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands and Dept. of Neurosurgery, Medical Center Haaglanden, The Hague, The Netherlands), Anna Piippo-Karjalainen (Department of Neurosurgery, Helsinki University Central Hospital), Matti Pirinen (Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland), Horia Ples (Department of Neurosurgery, Emergency County Hospital Timisoara, Timisoara, Romania), Suzanne Polinder (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Inigo Pomposo (Department of Neurosurgery, Hospital of Cruces, Bilbao, Spain), Jussi P Posti (Division of Clinical Neurosciences, Department of Neurosurgery and Turku Brain Injury Centre, Turku University Hospital and University of Turku, Turku, Finland), Louis Puybasset (Department of Anesthesiology and Critical Care, Pitié -Salpêtrière Teaching Hospital, Assistance Publique, Hôpitaux de Paris and University Pierre et Marie Curie, Paris, France), Andreea Radoi (Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Barcelona, Spain), Arminas Ragauskas (Department of Neurosurgery, Kaunas University of technology and Vilnius University, Vilnius, Lithuania), Rahul Raj (Department of Neurosurgery, Helsinki University Central Hospital), Malinka Rambadagalla (Department of Neurosurgery, Rezekne Hospital, Latvia), Jonathan Rhodes (Department of Anaesthesia, Critical Care & Pain Medicine NHS Lothian & University of Edinburg, Edinburgh, UK), Sylvia Richardson (Director, MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK), Sophie Richter (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Samuli Ripatti (Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland), Saulius Rocka (Department of Neurosurgery, Kaunas University of technology and Vilnius University, Vilnius, Lithuania), Cecilie Roe (Department of Physical Medicine and Rehabilitation, Oslo University Hospital/University of Oslo, Oslo, Norway), Olav Roise (Division of Orthopedics, Oslo University Hospital, Oslo, Norway; Institue of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway), Jonathan Rosand (Broad Institute, Cambridge MA Harvard Medical School, Boston MA, Massachusetts General Hospital, Boston MA, USA), Jeffrey V Rosenfeld (National Trauma Research Institute, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia), Christina Rosenlund (Department of Neurosurgery, Odense University Hospital, Odense, Denmark), Guy Rosenthal (Department of Neurosurgery, Hadassah-hebrew University Medical center, Jerusalem, Israel), Rolf Rossaint (Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany), Sandra Rossi (Department of Anesthesia & Intensive Care, Azienda Ospedaliera Università di Padova, Padova, Italy), Daniel Rueckert (Department of Computing, Imperial College London, London, UK), Martin Rusnák (International Neurotrauma Research Organisation, Vienna, Austria), Juan Sahuquillo (Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Barcelona, Spain), Oliver Sakowitz (Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany; Klinik für Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg, Germany), Renan Sanchez-Porras (Klinik für Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg, Germany), Janos Sandor (Division of Biostatistics and Epidemiology, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary), Nadine Schäfer (Institute of Research in Operative Medicine (IFOM), Witten/Herdecke University, Cologne, Germany), Silke Schmidt (8 Department Health and Prevention, University Greifswald, Greifswald, Germany), Herbert Schoechl (Department of Anaesthesiology and Intensive Care, AUVA Trauma Hospital, Salzburg, Austria), Guus Schoonman (Department of Neurology, Elisabeth-TweeSteden Ziekenhuis, Tilburg, the Netherlands), Rico Frederik Schou (Department of Neuroanesthesia and Neurointensive Care, Odense University Hospital, Odense, Denmark), Elisabeth Schwendenwein (Trauma Surgery, Medical University Vienna, Vienna, Austria), Charlie Sewalt (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Toril Skandsen (Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway), Peter Smielewski (Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Abayomi Sorinola (Department of Neurosurgery, University of Pécs, Pécs, Hungary), Emmanuel A Stamatakis (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Simon Stanworth (Oxford University Hospitals NHS Trust, Oxford, UK), Robert Stevens (Division of Neuroscience Critical Care, John Hopkins University School of Medicine, Baltimore, USA), William Stewart (Department of Neuropathology, Queen Elizabeth University Hospital and University of Glasgow, Glasgow, UK), Ewout W Steyerberg (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands; Dept. of Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands), Nino Stocchetti (Department of Pathophysiology and Transplantation, Milan University, and Neuroscience ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy), Nina Sundström (Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden), Anneliese Synnot (Australian & New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia; Cochrane Consumers and Communication Review Group, Centre for Health Communication and Participation, School of Psychology and Public Health, La Trobe University, Melbourne, Australia), Riikka Takala (Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku, Turku, Finland), Viktória Tamás (Department of Neurosurgery, University of Pécs, Pécs, Hungary), Tomas Tamosuitis (Department of Neurosurgery, Kaunas University of Health Sciences, Kaunas, Lithuania), Mark Steven Taylor (Department of Public Health, Faculty of Health Sciences and Social Work, Trnava University, Trnava, Slovakia), Braden Te Ao (National Institute for Stroke and Applied Neurosciences, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland, New Zealand), Olli Tenovuo (Division of Clinical Neurosciences, Department of Neurosurgery and Turku Brain Injury Centre, Turku University Hospital and University of Turku, Turku, Finland), Alice Theadom (National Institute for Stroke and Applied Neurosciences, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland, New Zealand), Matt Thomas (Intensive Care Unit, Southmead Hospital, Bristol, Bristol, UK), Dick Tibboel (Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands), Marjolein Timmers (Department of Intensive Care and Department of Ethics and Philosophy of Medicine, Erasmus Medical Center, Rotterdam, The Netherlands), Christos Tolias (Department of Neurosurgery, Kings college London, London, UK), Tony Trapani (ANZIC Research Centre, Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Victoria, Australia), Cristina Maria Tudora (Department of Neurosurgery, Emergency County Hospital Timisoara, Timisoara, Romania), Peter Vajkoczy (Neurologie, Neurochirurgie und Psychiatrie, Charité – Universitätsmedizin Berlin, Berlin, Germany), Shirley Vallance (ANZIC Research Centre, Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Victoria, Australia), Egils Valeinis (Neurosurgery clinic, Pauls Stradins Clinical University Hospital, Riga, Latvia), Zoltán Vámos (Department of Anaesthesiology and Intensive Therapy, University of Pécs, Pécs, Hungary), Mathieu van der Jagt (Department of Intensive Care Adults, Erasmus MC– University Medical Center Rotterdam, Rotterdam, the Netherlands), Gregory Van der Steen (Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium), Joukje van der Naalt (Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands), Jeroen T J M van Dijck (Dept. of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands; Dept. of Neurosurgery, Medical Center Haaglanden, The Hague, The Netherlands), Thomas A van Essen (Dept. of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands; Dept. of Neurosurgery, Medical Center Haaglanden, The Hague, The Netherlands), Wim VanHecke (icoMetrix NV, Leuven, Belgium), Caroline van Heugten (Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK), Dominique Van Praag (Psychology Department, Antwerp University Hospital, Edegem, Belgium), Thijs Vande Vyvere (icoMetrix NV, Leuven, Belgium), Roel P J van Wijk (Dept. of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands; Dept. of Neurosurgery, Medical Center Haaglanden, The Hague, The Netherlands), Alessia Vargiolu (NeuroIntensive Care, ASST di Monza, Monza, Italy), Emmanuel Vega (Department of Anesthesiology-Intensive Care, Lille University Hospital, Lille, France), Kimberley Velt (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Jan Verheyden (icoMetrix NV, Leuven, Belgium), Paul M Vespa (Director of Neurocritical Care, University of California, Los Angeles, USA), Anne Vik (Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; Department of Neurosurgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway), Rimantas Vilcinis (Department of Neurosurgery, Kaunas University of Health Sciences, Kaunas, Lithuania), Victor Volovici (Department of Neurosurgery, Erasmus MC, Rotterdam, the Netherlands), Nicole von Steinbüchel (Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany), Daphne Voormolen (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Petar Vulekovic (Department of Neurosurgery, Clinical centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia), Kevin K W Wang (Department of Emergency Medicine, University of Florida, Gainesville, Florida, USA), Eveline Wiegers (Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands), Guy Williams (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Lindsay Wilson (Division of Psychology, University of Stirling, Stirling, UK), Stefan Winzeck (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK), Stefan Wolf (Department of Neurosurgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany), Zhihui Yang (Department of Emergency Medicine, University of Florida, Gainesville, Florida, USA), Peter Ylén (VTT Technical Research Centre, Tampere, Finland), Alexander Younsi (Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany), Frederick A Zeiler (Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; Section of Neurosurgery, Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada), Veronika Zelinkova (Department of Public Health, Faculty of Health Sciences and Social Work, Trnava University, Trnava, Slovakia), Agate Ziverte (Neurosurgery clinic, Pauls Stradins Clinical University Hospital, Riga, Latvia), Tommaso Zoerle (Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy).

    • Contributors Study concept: LW, DM, LH, KK, BJS, VFJN and EAS. Analysis and interpretation of data: LW, LH, KK, BJS, VFJN, NvS, AM and DM. Drafting the manuscript: LW, DM, BJS and VFJN. Critical revision of the manuscript for intellectual content: LW, LH, KK, BJS, VFJN, EAS, NvS, KC, AC, AM and DM. All authors read and approved the final draft of the manuscript.

    • Funding Data used in preparation of this manuscript were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework programme (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA). Data for the CENTER-TBI study have been collected through the Quesgen e-CRF (Quesgen Systems, USA), hosted on the INCF platform and extracted via the INCF Neurobot tool (INCF, Sweden).

    • Competing interests LW, LH, KK, NvS, DvP, AM and DM report funding from the EU FP7 programme during the course of the study. LW reports grants and personal fees from Vasopharm, outside the submitted work; BJS reports personal fees from Cassava Sciences, Greenfield BioVentures, and Cambridge Cognition, outside the submitted work; VFJN reports grants from Roche, outside the submitted work. DM reports grants, personal fees and non-financial support from GlaxoSmithKline, grants and personal fees from NeuroTrauma Sciences, Lantmannen AB and Integra Neurosciences, and personal fees from Pfizer, Calico and PressuraNeuro, outside the submitted work.

    • Patient consent for publication Not required.

    • Ethics approval Ethical approval was obtained for each recruiting site, and consent was obtained in all patients according to national and local procedures. A complete ethics statement can be found at https://www.center-tbi.eu/project/ethical-approval.

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

    • Data availability statement Data are available upon reasonable request. Data sharing statement: will individual participant data be available? 'Yes, including data dictionary. What other documents will be available? Study protocol, analytic code and analysis scripts. When will data be available? Immediately following publication, conditional to approved study proposal; no end date. With whom? Researchers who provide a methodologically sound study proposal that is approved by the management committee. For what type of analyses? To achieve the aims in the approved proposal. By what mechanism will data be made available? Proposals may be submitted online https://www.center-tbi.eu/data. A Data Access Agreement is required, and all access must comply with regulatory restrictions imposed on the original study.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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