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

Marc A Khoury; Nathan W Churchill; Alex Di Battista; Simon J Graham; Sean Symons; Angela K Troyer; Angela Roberts; Sanjeev Kumar; Brian Tan; Stephen R Arnott; Joel Ramirez; Maria C Tartaglia; Michael Borrie; Bruce Pollock; Tarek K Rajji; Stephen H Pasternak; Andrew Frank; David F Tang-Wai; Christopher J M Scott; Seyyed Mohammad Hassan Haddad; Nuwan Nanayakkara; Joseph B Orange; Alicia Peltsch; Corinne E Fischer; David G Munoz; Tom A Schweizer

doi:10.1007/s00415-024-12369-2

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

J Neurol. 2024 May 8. doi: 10.1007/s00415-024-12369-2. Online ahead of print.

Authors

Marc A Khoury^{1

2}, Nathan W Churchill^{3

4}, Alex Di Battista^{5

6}, Simon J Graham^{7

8

9}, Sean Symons¹⁰, Angela K Troyer¹¹, Angela Roberts^{12

13

14}, Sanjeev Kumar^{15

16}, Brian Tan¹⁷, Stephen R Arnott¹⁷, Joel Ramirez¹⁸, Maria C Tartaglia¹⁹, Michael Borrie^{20

21}, Bruce Pollock^{15

16}, Tarek K Rajji^{15

16}, Stephen H Pasternak^{21

22}, Andrew Frank^{23

24}, David F Tang-Wai²⁵, Christopher J M Scott^{18

26

8}, Seyyed Mohammad Hassan Haddad²⁷, Nuwan Nanayakkara²⁷, Joseph B Orange^{12

27}, Alicia Peltsch²⁸, Corinne E Fischer^{3

29

16}, David G Munoz^{3

29

30}, Tom A Schweizer^{3

29

31

32}

Affiliations

¹ Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. marc.khoury@mail.utoronto.ca.
² Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. marc.khoury@mail.utoronto.ca.
³ Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
⁴ Physics Department, Toronto Metropolitan University, Toronto, Canada.
⁵ Defence Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada.
⁶ Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Canada.
⁷ Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, M4N 3M5, Canada.
⁸ Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.
⁹ Department of Medical Biophysics, University of Toronto, Toronto, Canada.
¹⁰ Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹¹ Neuropsychology and Cognitive Health Program, Baycrest Hospital, Department of Psychology, University of Toronto, Toronto, ON, Canada.
¹² School of Communication Sciences and Disorders, Western University, London, ON, Canada.
¹³ Department of Computer Science, Western University, London, ON, Canada.
¹⁴ Canadian Centre for Activity and Aging, London, ON, Canada.
¹⁵ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
¹⁶ Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁷ Rotman Research Institute, Baycrest Health Sciences, Toronto, ON, Canada.
¹⁸ Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
²⁰ Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
²¹ . Joseph's Healthcare Centre, London, ON, Canada.
²² Department of Clinical Neurological Sciences, London Health Sciences Centre, London, ON, Canada.
²³ Bruyère Research Institute, Ottawa, ON, Canada.
²⁴ University of Ottawa, Ottawa, ON, Canada.
²⁵ Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
²⁶ L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁷ University of Western, London, ON, Canada.
²⁸ Queen's University, Kingston, ON, Canada.
²⁹ Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
³⁰ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
³¹ Institute for Biomedical Engineering, Science & Tech (iBEST), A Partnership Between St. Michael's Hospital and Ryerson University, Toronto, ON, M5V 1T8, Canada.
³² Division of Neurosurgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

PMID: 38717612
DOI: 10.1007/s00415-024-12369-2

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.

Keywords: Bayesian statistics; Magnetic resonance imaging (MRI); Mild-cognitive-impairment (MCI); Neurodegeneration; Traumatic brain injury (TBI).