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Traumatic brain injury fast-forwards Alzheimer’s pathology: evidence from amyloid positron emission tomorgraphy imaging

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Abstract

Purpose

Traumatic brain injury (TBI) has been proposed as a risk factor for Alzheimer’s disease (AD), although the mechanisms underlying the putative association are poorly understood. We investigated elderly individuals with a remote history of TBI, aiming to understand how this may have influenced amyloidosis, neurodegeneration, and clinical expression along the AD continuum.

Methods

Total of 241 individual datasets including amyloid beta (Aβ) positron emission tomography ([18F]-AV45), structural MRI, and neuropsychological measures, were obtained from the Alzheimer’s Disease Neuroimaging Initiative. The data were stratified into groups with (TBI +) or without (TBI −) history of head injury, and by clinical dementia rating (CDR) scores, into subgroups with normal cognition (CDR = 0) and those with symptomatic cognitive decline (CDR ≥ 0.5). We contrasted the TBI + and TBI − subgroups with respect to the onset age and extent of cognitive decline, cortical thickness changes, and Aβ standard uptake value (SUVr).

Results

Compared to the TBI −/CDR ≥ 0.5 subgroup, the TBI + /CDR ≥ 0.5 subgroup showed a 3–4 year earlier age of cognitive impairment onset (ACIO, p = 0.005). Among those participants on the AD continuum (Aβ + , as defined by a cortical SUVr ≥ 1.23), irrespective of current CDR, a TBI + history was associated with greater Aβ deposition and more pronounced cortical thinning. When matched for severity of cognitive status, the TBI + /CDR ≥ 0.5 group showed greater Aβ burden, but earlier ACIO as compared to the TBI −/CDR ≥ 0.5, suggesting a more indolent clinical AD progression in those with TBI history.

Conclusion

Remote TBI history may alter the AD onset trajectory, with approximately 4 years earlier ACIO, greater amyloid deposition, and cortical thinning.

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Data availability

The original data used in this project and that support the findings of this study are openly available through (https://ida.loni.usc.edu), upon approval from the ADNI project administration.

Code availability

The different software packages used in the preparation of this manuscript are publicly available. In addition, the codes used for the analysis of the data are available upon request from the corresponding author.

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Acknowledgements

The authors would like to acknowledge ADNI contributors listed at http://adni.loni.usc.edu/data-samples/access-data/groups-acknowledgements-journal-format/. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

Funding

This research was supported by Motor Accident Insurance Commission (MAIC), The Queensland Government, Australia (Grant number: 2014000857). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (US Department of Defense award number W81XWH-12-2-0012).

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Authors and Affiliations

  1. The Queensland Brain Institute, The University of Queensland, Building 79, Upland Road, Saint Lucia, Brisbane, QLD, 4072, Australia

    Abdalla Z. Mohamed, Peter J. Nestor & Fatima A. Nasrallah

  2. Thompson Institute, University of The Sunshine Coast, Birtinya, QLD, 4575, Australia

    Abdalla Z. Mohamed

  3. Mater Hospital, South Brisbane, QLD, 4101, Australia

    Peter J. Nestor

  4. Department of Nuclear Medicine, Inselspital, Bern University, Bern, Switzerland

    Paul Cumming

  5. School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia

    Paul Cumming

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  1. Abdalla Z. Mohamed
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  2. Peter J. Nestor
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  3. Paul Cumming
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  4. Fatima A. Nasrallah
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for the Alzheimer’s Disease Neuroimaging Initiative

Contributions

AZM, PN, and FN decided on the study concept and design. ADNI project members collected the data used in the preparation of the manuscript. AZM performed the data analysis and wrote the manuscript. FN, PC, and PN read the manuscript and provided a critical feedback on the results and the written manuscript.

Corresponding author

Correspondence to Fatima A. Nasrallah.

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Conflict of interest

The authors report no competing interests.

Ethical approval

This research involves de-identified human data collected by ADNI project. This study obtained ethics approval to use de-identified data from the Human Research Ethics Committee of the University of Queensland, Australia (IRB number #2017000630).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

No individuals’ information was used in the preparation of any of the figures. All data used in the preparation of the manuscript were of group levels, without any individual images or personal information used in the preparation of the manuscript.

Additional information

For the Alzheimer’s Disease Neuroimaging Initiative: Data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Mohamed, A.Z., Nestor, P.J., Cumming, P. et al. Traumatic brain injury fast-forwards Alzheimer’s pathology: evidence from amyloid positron emission tomorgraphy imaging. J Neurol 269, 873–884 (2022). https://doi.org/10.1007/s00415-021-10669-5

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