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Neurology
Protocol
ADVANCE-TBI study protocol: traumatic brain injury outcomes in UK military personnel serving in Afghanistan between 2003 and 2014 – a longitudinal cohort study
  1. Neil S N Graham1,2,
  2. Grace Blissitt3,4,
  3. Karl Zimmerman1,2,
  4. Daniel Friedland1,
  5. Marc-Emmanuel Dumas3,5,
  6. Emma Coady3,4,
  7. Amanda Heslegrave6,7,
  8. Henrik Zetterberg6,7,
  9. Valentina Escott-Price8,9,
  10. Susie Schofield3,
  11. Nicola T Fear10,11,
  12. Christopher Boos3,11,
  13. Anthony M J Bull12,13,
  14. Paul Cullinan3,
  15. Alexander Bennett3,4,
  16. David J Sharp1,2
  17. for the ADVANCE Study
  1. 1Department of Brain Sciences, Imperial College London, London, UK
  2. 2UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK
  3. 3National Heart and Lung Institute, Imperial College London, London, UK
  4. 4Academic Department of Military Rehabilitation, Defence Medical Rehabilitation Centre, Loughborough, UK
  5. 5Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
  6. 6Institute of Neurology, UCL Queen Square, London, UK
  7. 7UK Dementia Research Institute, University College London, London, UK
  8. 8Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
  9. 9UK Dementia Research Institute, Cardiff University, Cardiff, UK
  10. 10King's Centre for Military Health Research, King's College London, London, UK
  11. 11Academic Department for Military Mental Health, King's College London, London, UK
  12. 12Centre for Injury Studies, Imperial College London, London, UK
  13. 13Department of Bioengineering, Imperial College London, London, UK
  1. Correspondence to Professor David J Sharp; david.sharp{at}imperial.ac.uk

Abstract

Introduction Outcomes of traumatic brain injury (TBI) are highly variable, with cognitive and psychiatric problems often present in survivors, including an increased dementia risk in the long term. Military personnel are at an increased occupational risk of TBI, with high rates of complex polytrauma including TBI characterising the UK campaign in Afghanistan. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE)-TBI substudy will describe the patterns, associations and long-term outcomes of TBI in the established ADVANCE cohort.

Methods and analysis The ADVANCE cohort comprises 579 military personnel exposed to major battlefield trauma requiring medical evacuation, and 566 matched military personnel without major trauma. TBI exposure has been captured at baseline using a standardised interview and registry data, and will be refined at first follow-up visit with the Ohio State Method TBI interview (a National Institute of Neurological Disorders and Stroke TBI common data element). Participants will undergo blood sampling, MRI and detailed neuropsychological assessment longitudinally as part of their follow-up visits every 3–5 years over a 20-year period. Biomarkers of injury, neuroinflammation and degeneration will be quantified in blood, and polygenic risk scores calculated for neurodegeneration. Age-matched healthy volunteers will be recruited as controls for MRI analyses. We will describe TBI exposure across the cohort, and consider any relationship with advanced biomarkers of injury and clinical outcomes including cognitive performance, neuropsychiatric symptom burden and function. The influence of genotype will be assessed. This research will explore the relationship between military head injury exposure and long-term outcomes, providing insights into underlying disease mechanisms and informing prevention interventions.

Ethics and dissemination The ADVANCE-TBI substudy has received a favourable opinion from the Ministry of Defence Research Ethics Committee (ref: 2126/MODREC/22). Findings will be disseminated via publications in peer-reviewed journals and presentations at conferences.

  • neurology
  • dementia
  • trauma management
  • Magnetic Resonance Imaging
  • neurological injury
  • neurosurgery
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2022-069243

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    Footnotes

    • Twitter @nsngraham

    • Contributors DJS, AMJB, PC, CB, NTF, NSNG and KZ were involved in the design and conception of the study and protocol. The first draft was prepared by GB and NSNG. DJS, AMJB, KZ and SS revised initial iterations. SS provided statistical review. NSNG, GB, KZ, DF, M-ED, EC, AH, HZ, VE-P, SS, NTF, CB, AMJB, PC, AB and DJS reviewed and approved the final version of the manuscript.

    • Funding ADVANCE-TBI is funded by the ADVANCE Charity (award/grant number: NA). Key contributors to the ADVANCE Charity include Headley Court Charity (principal funder), HM Treasury (LIBOR Grant), Help for Heroes, Nuffield Trust for the Forces of the Crown, Forces in Mind Trust, National Lottery Community Fund, Blesma—The Limbless Veterans and the UK Ministry of Defence (award/grant number: NA).

    • Competing interests HZ has served at scientific advisory boards and/or as a consultant for AbbVie, Alector, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Pinteon Therapeutics, Red Abbey Labs, reMYND, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen and Roche; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). DJS provides medicolegal services and serves on the Rugby Football Union concussion advisory board.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

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