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History of traumatic brain injury is associated with increased grey-matter loss in patients with mild cognitive impairment

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Abstract

Objectives

To investigate whether a history of traumatic brain injury (TBI) is associated with greater long-term grey-matter loss in patients with mild cognitive impairment (MCI).

Methods

85 patients with MCI were identified, including 26 with a previous history of traumatic brain injury (MCI[TBI-]) and 59 without (MCI[TBI+]). Cortical thickness was evaluated by segmenting T1-weighted MRI scans acquired longitudinally over a 2-year period. Bayesian multilevel modelling was used to evaluate group differences in baseline cortical thickness and longitudinal change, as well as group differences in neuropsychological measures of executive function.

Results

At baseline, the MCI[TBI+] group had less grey matter within right entorhinal, left medial orbitofrontal and inferior temporal cortex areas bilaterally. Longitudinally, the MCI[TBI+] group also exhibited greater longitudinal declines in left rostral middle frontal, the left caudal middle frontal and left lateral orbitofrontal areas sover the span of 2 years (median = 1–2%, 90%HDI [−0.01%: −0.001%], probability of direction (PD) = 90–99%). The MCI[TBI+] group also displayed greater longitudinal declines in Trail-Making-Test (TMT)-derived ratio (median: 0.737%, 90%HDI: [0.229%: 1.31%], PD = 98.8%) and differences scores (median: 20.6%, 90%HDI: [−5.17%: 43.2%], PD = 91.7%).

Conclusions

Our findings support the notion that patients with MCI and a history of TBI are at risk of accelerated neurodegeneration, displaying greatest evidence for cortical atrophy within the left middle frontal and lateral orbitofrontal frontal cortex. Importantly, these results suggest that long-term TBI-mediated atrophy is more pronounced in areas vulnerable to TBI-related mechanical injury, highlighting their potential relevance for diagnostic forms of intervention in TBI.

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Acknowledgements

The authors acknowledge ONDRI’s participants, clinical coordinators, and other research team members including Catarina Downey, Heather Hink, Donna McBain, Lindsey McLeish, and Alicia J. Peltsch. This research was conducted with the support of the Ontario Brain Institute, an independent non-profit corporation, funded partially by the Ontario government. The opinions, results, and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred. Matching funds were provided by participant hospital (recruitment sites) and research institute foundations, including the Baycrest Foundation, Bruyère Research Institute, Centre for Addiction and Mental Health Foundation, London Health Sciences Foundation, McMaster University Faculty of Health Sciences, Ottawa Brain and Mind Research Institute, Queen’s University Faculty of Health Sciences, the Sunnybrook Foundation, the Thunder Bay Regional Health Sciences Centre, the University of Ottawa Faculty of Medicine, and the Windsor/Essex County ALS Association. The Temerty Family Foundation provided the major infrastructure matching funds.

Funding

Angela Christine Roberts: (1) Salary support from the Canada Research Chairs program. (2) Travel stipends from the Movement Disorders Society and World Parkinson Congress. Sanjeev Kumar: (1) Research support from Brain and Behavior Foundation, National institute on Ageing, BrightFocus Foundation, Brain Canada, Canadian Institute of Health Research, Canadian Consortium on Neurodegeneration in Aging, Centre for Ageing and Brain Health Innovation, Centre for Addiction and Mental Health, and an Academic Scholars Award from the Department of Psychiatry, University of Toronto. Equipment support from Soterix Medical. Stephen R. Arnott: (1) Consultation work for Indoc Research. Maria C. Tartaglia: (1) NIH, Weston Brain Foundation, Tanenbaum Institute for Science in Sport. (2) Consultant: Eli Lilly, EISAI. (3) Scientific advisor Women’s Brain Project, Brain Injury Canada, PSP Canada. (4) Clinical trials: Passage Bio, Janssen, Biogen, Avanex, Green Valley, Roche, GSK, BMS. Bruce Pollock: (1) Dr. Bruce G. Pollock receives research support from the Peter & Shelagh Godsoe Endowed Chair in Late-Life Mental Health, CAMH Foundation, and Discovery Fund, National Institute of Aging, Brain Canada, the Canadian Institutes of Health Research, the Alzheimer’s Drug Discovery Foundation, the Ontario Brain Institute, the Centre for Aging and Brain Health Innovation, the Bright Focus Foundation, the Alzheimer’s Society of Canada, the W. Garfield Weston Foundation, the Weston Brain Institute, the Canadian Consortium on Neurodegeneration in Aging and Genome Canada. Dr. Pollock receives honoraria from the American Geriatrics Society for book authorship and holds United States Provisional Patent Nos. 6/490,680, 17/396,030 and Canadian Provisional Patent No. 3,054,093 for a cell-based assay and kits for assessing serum anticholinergic activity. Tarek K. Rajji: (1) Dr. Rajji has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute. Dr. Rajji also received for an investigator-initiated study in-kind equipment support from Newronika, and in-kind research online accounts from Scientific Brain Training Pro, and participated in 2021 and 2022 in an advisory activity for Biogen Canada Inc. As of September 1, 2023, Dr. Rajji is an ex officio member of the Board of Trustees of the Centre for Addiction and Mental Health (CAMH) in his role as Chair of the Medical Advisory Committee at CAMH. Dr. Rajji is also an inventor on the United States Provisional Patent No. 17/396,030 that describes cell-based assays and kits for assessing serum cholinergic receptor activity. David F. Tang-Wai: (1) Hydrocephalus Canada medical advisory board. Corinne E. Fischer: (1) Grant Funding For: NIH, NIA, CCNA, CIHR, St. Michaels Hospital Foundation, Hilary and Galen Weston Foundation, ADDF and Novo Nordisk.

Author information

Authors and Affiliations

  1. Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

    Marc A. Khoury, Nathan W. Churchill, Corinne E. Fischer, David G. Munoz & Tom A. Schweizer

  2. Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Marc A. Khoury, Corinne E. Fischer, David G. Munoz & Tom A. Schweizer

  3. Defence Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada

    Alex Di Battista

  4. Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, M4N 3M5, Canada

    Simon J. Graham

  5. Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Sean Symons

  6. Neuropsychology and Cognitive Health Program, Baycrest Hospital, Department of Psychology, University of Toronto, Toronto, ON, Canada

    Angela K. Troyer

  7. School of Communication Sciences and Disorders, Western University, London, ON, Canada

    Angela Roberts & Joseph B. Orange

  8. Department of Computer Science, Western University, London, ON, Canada

    Angela Roberts

  9. Canadian Centre for Activity and Aging, London, ON, Canada

    Angela Roberts

  10. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Sanjeev Kumar, Bruce Pollock & Tarek K. Rajji

  11. Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Sanjeev Kumar, Bruce Pollock, Tarek K. Rajji & Corinne E. Fischer

  12. Rotman Research Institute, Baycrest Health Sciences, Toronto, ON, Canada

    Brian Tan & Stephen R. Arnott

  13. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Joel Ramirez & Christopher J. M. Scott

  14. Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada

    Maria C. Tartaglia

  15. Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

    Michael Borrie

  16. . Joseph’s Healthcare Centre, London, ON, Canada

    Michael Borrie & Stephen H. Pasternak

  17. Department of Clinical Neurological Sciences, London Health Sciences Centre, London, ON, Canada

    Stephen H. Pasternak

  18. Bruyère Research Institute, Ottawa, ON, Canada

    Andrew Frank

  19. University of Ottawa, Ottawa, ON, Canada

    Andrew Frank

  20. Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada

    David F. Tang-Wai

  21. L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Christopher J. M. Scott

  22. University of Western, London, ON, Canada

    Seyyed Mohammad Hassan Haddad, Nuwan Nanayakkara & Joseph B. Orange

  23. Queen’s University, Kingston, ON, Canada

    Alicia Peltsch

  24. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    David G. Munoz

  25. Institute for Biomedical Engineering, Science & Tech (iBEST), A Partnership Between St. Michael’s Hospital and Ryerson University, Toronto, ON, M5V 1T8, Canada

    Tom A. Schweizer

  26. Division of Neurosurgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Tom A. Schweizer

  27. Physics Department, Toronto Metropolitan University, Toronto, Canada

    Nathan W. Churchill

  28. Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Canada

    Alex Di Battista

  29. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada

    Simon J. Graham & Christopher J. M. Scott

  30. Department of Medical Biophysics, University of Toronto, Toronto, Canada

    Simon J. Graham

Authors
  1. Marc A. Khoury
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  2. Nathan W. Churchill
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  3. Alex Di Battista
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  4. Simon J. Graham
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  5. Sean Symons
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  6. Angela K. Troyer
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  7. Angela Roberts
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  8. Sanjeev Kumar
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  9. Brian Tan
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  10. Stephen R. Arnott
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  11. Joel Ramirez
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  12. Maria C. Tartaglia
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  13. Michael Borrie
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  14. Bruce Pollock
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  15. Tarek K. Rajji
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  16. Stephen H. Pasternak
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  17. Andrew Frank
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  18. David F. Tang-Wai
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  19. Christopher J. M. Scott
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  20. Seyyed Mohammad Hassan Haddad
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  21. Nuwan Nanayakkara
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  22. Joseph B. Orange
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  23. Alicia Peltsch
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  24. Corinne E. Fischer
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  25. David G. Munoz
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  26. Tom A. Schweizer
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Corresponding author

Correspondence to Marc A. Khoury.

Ethics declarations

Conflicts of interest

The following authors have no conflicts of interest/disclosures: Marc A. Khoury, Nathan W. Churchill, Alex Di Battista, Simon J. Graham, Sean Symons, Angela K. Troyer, Brian Tan, Joel Ramirez, Stephen H. Pasternak, Michael Borrie, Andrew Frank, Michaels Borrie, Christopher J. M. Scott, Seyyed Mohammad Hassan Haddad, Nuwan Nanayakkara, Joseph B. Orange, Alicia Peltsch, David G. Munoz, Tom A. Schweizer.

Ethical standards

All the procedures have been completed in compliance with the ethical standards of the Committee on Human Experimentation of the institution under the accord of the Helsinki Declaration of 1975. No animal experiments were undertaken for this study.

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Khoury, M.A., Churchill, N.W., Di Battista, A. et al. History of traumatic brain injury is associated with increased grey-matter loss in patients with mild cognitive impairment. J Neurol (2024). https://doi.org/10.1007/s00415-024-12369-2

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  • DOI: https://doi.org/10.1007/s00415-024-12369-2

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