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Investigating the relationship between mild traumatic brain injury and Alzheimer’s disease and related dementias: a systematic review

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Abstract

The objective of this systematic review is to synthesize the relevant literature published after 2016 to ascertain the current landscape of science that relates mild traumatic brain injury (mTBI) to the onset of Alzheimer’s disease and related dementias (ADRD) and identify areas of need for future research. We conducted database searches and retrieved articles that were published after 2016 that utilized cognitive assessments to understand the relationship between mTBI and ADRD. We identified eight relevant articles in the review process, four of which presented a significant relationship between mTBI and disease or cognitive impairment outcomes. The studies included in this systematic review underscore the need for future research investigating a possible causal relationship between mTBI and ADRDs given the high prevalence of mTBI among brain injury patients and the lack of literature specifically addressing this issue. Future research should standardize the definitions of mTBI, AD, and ADRDs to create reliable and reproducible results that more comprehensively capture the nuances of this relationship.

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References

  1. Matthews KA, Xu W, Gaglioti AH et al (2019) Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥65 years. Alzheimers Dement 15:17–24. https://doi.org/10.1016/j.jalz.2018.06.3063

    Article  PubMed  Google Scholar 

  2. Bazarian JJ, Cernak I, Noble-Haeusslein L et al (2009) Long-term neurologic outcomes after traumatic brain injury. J Head Trauma Rehabil 24:439–451. https://doi.org/10.1097/HTR.0b013e3181c15600

    Article  PubMed  Google Scholar 

  3. Fleminger S (2003) Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry 74:857–862. https://doi.org/10.1136/jnnp.74.7.857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Luukinen H, Viramo P, Herala M et al (2005) Fall-related brain injuries and the risk of dementia in elderly people: a population-based study. Eur J Neurol 12:86–92. https://doi.org/10.1111/j.1468-1331.2004.00953.x

    Article  CAS  PubMed  Google Scholar 

  5. Mortimer JA, Van Duijn CM, Chandra V et al (1991) Head trauma as a risk factor for alzheimer’s disease: a collaborative re-analysis of case-control studies. Int J Epidemiol 20:S28–S35. https://doi.org/10.1093/ije/20.Supplement_2.S28

    Article  PubMed  Google Scholar 

  6. Sivanandam TM, Thakur MK (2012) Traumatic brain injury: a risk factor for Alzheimer’s disease. Neurosci Biobehav Rev 36:1376–1381. https://doi.org/10.1016/j.neubiorev.2012.02.013

    Article  PubMed  Google Scholar 

  7. Helmes E, Østbye T, Steenhuis RE (2011) Incremental contribution of reported previous head injury to the prediction of diagnosis and cognitive functioning in older adults. Brain Inj 25:338–347. https://doi.org/10.3109/02699052.2011.556104

    Article  PubMed  Google Scholar 

  8. van Duijn CM, Tanja TA, Haaxma R et al (1992) Head trauma and the risk of alzheimer’s disease. Am J Epidemiol 135:775–782. https://doi.org/10.1093/oxfordjournals.aje.a116364

    Article  PubMed  Google Scholar 

  9. Godbolt AK, Cancelliere C, Hincapié CA et al (2014) Systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury: results of the international collaboration on mild traumatic brain injury prognosis. Arch Phys Med Rehabil 95:S245–S256. https://doi.org/10.1016/j.apmr.2013.06.036

    Article  PubMed  Google Scholar 

  10. Julien J, Joubert S, Ferland M-C et al (2017) Association of traumatic brain injury and Alzheimer disease onset: a systematic review. Ann Phys Rehabil Med 60:347–356. https://doi.org/10.1016/j.rehab.2017.03.009

    Article  CAS  PubMed  Google Scholar 

  11. Perry DC, Sturm VE, Peterson MJ et al (2016) Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis. J Neurosurg 124:511–526. https://doi.org/10.3171/2015.2.JNS14503

    Article  PubMed  Google Scholar 

  12. Mendez MF, Paholpak P, Lin A et al (2015) Prevalence of traumatic brain injury in early versus late-onset alzheimer’s disease. J Alzheimers Dis JAD 47:985–993. https://doi.org/10.3233/JAD-143207

    Article  PubMed  Google Scholar 

  13. Didehbani N, Fields LM, Wilmoth K et al (2020) Mild cognitive impairment in retired professional football players with a history of mild traumatic brain injury: a pilot investigation. Cogn Behav Neurol 33:208–217. https://doi.org/10.1097/WNN.0000000000000240

    Article  PubMed  PubMed Central  Google Scholar 

  14. June D, Williams OA, Huang C-W et al (2020) Lasting consequences of concussion on the aging brain: findings from the Baltimore Longitudinal Study of Aging. Neuroimage. https://doi.org/10.1016/j.neuroimage.2020.117182

    Article  PubMed  Google Scholar 

  15. Hayes JP, Logue MW, Sadeh N et al (2017) Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer’s disease. Brain. https://doi.org/10.1093/brain/aww344

    Article  PubMed  PubMed Central  Google Scholar 

  16. Yang S-T, Hsiao I-T, Hsieh C-J et al (2015) Accumulation of amyloid in cognitive impairment after mild traumatic brain injury. J Neurol Sci 349:99–104. https://doi.org/10.1016/j.jns.2014.12.032

    Article  CAS  PubMed  Google Scholar 

  17. Rostowsky KA, Irimia A, For the Alzheimer’s Disease Neuroimaging Initiative (2021) Acute cognitive impairment after traumatic brain injury predicts the occurrence of brain atrophy patterns similar to those observed in Alzheimer’s disease. GeroScience 43:2015–2039. https://doi.org/10.1007/s11357-021-00355-9

    Article  PubMed  PubMed Central  Google Scholar 

  18. Barnes DE, Byers AL, Gardner RC et al (2018) Association of mild traumatic brain injury with and without loss of consciousness with dementia in US military veterans. JAMA Neurol 75:1055. https://doi.org/10.1001/jamaneurol.2018.0815

    Article  PubMed  PubMed Central  Google Scholar 

  19. Petersen RC, Roberts RO, Knopman DS et al (2010) Prevalence of mild cognitive impairment is higher in men: the Mayo Clinic Study of Aging. Neurology 75:889–897. https://doi.org/10.1212/WNL.0b013e3181f11d85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li W, Risacher SL, McAllister TW, Saykin AJ (2016) Traumatic brain injury and age at onset of cognitive impairment in older adults. J Neurol 263:1280–1285. https://doi.org/10.1007/s00415-016-8093-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Albrecht MA, Masters CL, Ames D, Foster JK (2016) Impact of mild head injury on neuropsychological performance in healthy older adults: longitudinal assessment in the AIBL cohort. Front Aging Neurosci. https://doi.org/10.3389/fnagi.2016.00105

    Article  PubMed  PubMed Central  Google Scholar 

  22. Petersen RC (2018) How early can we diagnose Alzheimer disease (and is it sufficient)? The 2017 Wartenberg lecture. Neurology 91:395–402. https://doi.org/10.1212/WNL.0000000000006088

    Article  PubMed  PubMed Central  Google Scholar 

  23. Bateman RJ, Barthélemy NR, Horie K (2020) Another step forward in blood-based diagnostics for Alzheimer’s disease. Nat Med 26:314–316. https://doi.org/10.1038/s41591-020-0797-4

    Article  CAS  PubMed  Google Scholar 

  24. Wang M-L, Wei X-E, Yu M-M et al (2017) Self-reported traumatic brain injury and in vivo measure of AD-vulnerable cortical thickness and AD-related biomarkers in the ADNI cohort. Neurosci Lett 655:115–120. https://doi.org/10.1016/j.neulet.2017.06.055

    Article  CAS  PubMed  Google Scholar 

  25. Lucke-Wold BP, Smith KE, Nguyen L et al (2015) Sleep disruption and the sequelae associated with traumatic brain injury. Neurosci Biobehav Rev 55:68–77. https://doi.org/10.1016/j.neubiorev.2015.04.010

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ma H-P, Ou J-C, Yeh C-T et al (2014) Recovery from sleep disturbance precedes that of depression and anxiety following mild traumatic brain injury: a 6-week follow-up study. BMJ Open 4:e004205. https://doi.org/10.1136/bmjopen-2013-004205

    Article  PubMed  PubMed Central  Google Scholar 

  27. Alosco ML, Stern RA (2019) The long-term consequences of repetitive head impacts: chronic traumatic encephalopathy. Handb Clin Neurol 167:337–355. https://doi.org/10.1016/B978-0-12-804766-8.00018-2

    Article  PubMed  Google Scholar 

  28. Turner RC, Lucke-Wold BP, Robson MJ et al (2016) Alzheimer’s disease and chronic traumatic encephalopathy: distinct but possibly overlapping disease entities. Brain Inj 30:1279–1292. https://doi.org/10.1080/02699052.2016.1193631

    Article  PubMed  PubMed Central  Google Scholar 

  29. Washington PM, Villapol S, Burns MP (2016) Polypathology and dementia after brain trauma: does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy? Exp Neurol 275:381–388. https://doi.org/10.1016/j.expneurol.2015.06.015

    Article  PubMed  Google Scholar 

  30. Gavett BE, Stern RA, Cantu RC et al (2010) Mild traumatic brain injury: a risk factor for neurodegeneration. Alzheimers Res Ther 2:18. https://doi.org/10.1186/alzrt42

    Article  PubMed  PubMed Central  Google Scholar 

  31. Carroll L, Cassidy JD, Holm L et al (2004) Methodological issues and research recommendations for mild traumatic brain injury: the who collaborating centre task force on mild traumatic brain injury. J Rehabil Med 36:113–125. https://doi.org/10.1080/16501960410023877

    Article  Google Scholar 

  32. Jennett B (2005) Development of Glasgow coma and outcome scales. Nepal J Neurosci 2:24–28. https://doi.org/10.3126/njn.v2i1.19978

    Article  Google Scholar 

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Funding

NIA K-01 Award Grant #1 K01 AG054762-01A1.

Author information

Authors and Affiliations

  1. University of California, Berkeley, USA

    Emma Clark

  2. School of Medicine, University of Pittsburgh, Pittsburgh, USA

    Saurab Faruque

  3. School of Medicine, Wayne State University, Detroit, USA

    Cedric Mutebi

  4. School of Medicine and Health Sciences, The George Washington University, Washington, USA

    Newton V. Nagirimadugu

  5. School of Public Health, Yale University, New Haven, USA

    Alyssa Kim

  6. The George Washington University, Washington, USA

    Malavika Mahendran

  7. Lee Health, Fort Myers, USA

    Elaine Sullo

  8. Department of Psychiatry, Duke University, Durham, USA

    Rajendra Morey

  9. Department of Clinical Research and Leadership, School of Medicine and Health Sciences, The George Washington University, Washington, USA

    Robert W. Turner II

  10. Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Robert W. Turner II

Authors
  1. Emma Clark
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  2. Saurab Faruque
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  3. Cedric Mutebi
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  4. Newton V. Nagirimadugu
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  5. Alyssa Kim
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  6. Malavika Mahendran
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  7. Elaine Sullo
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  8. Rajendra Morey
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  9. Robert W. Turner II
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Contributions

RWT conceptualized this systematic review. ES, EC, CM, AK, and SF created the search strategy, exclusion criteria, and methodology. EC and AK screened and selected studies, performed quality assessment, assessed bias, and performed data extraction. All authors discussed the results of the selected studies. EC, CM, AK, and NVN created the initial draft. RWT, RM, EC, NVN, AK, and CM critically reviewed and revised the manuscript. The team was supervised by RWT.

Corresponding author

Correspondence to Robert W. Turner II.

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Clark, E., Faruque, S., Mutebi, C. et al. Investigating the relationship between mild traumatic brain injury and Alzheimer’s disease and related dementias: a systematic review. J Neurol 269, 4635–4645 (2022). https://doi.org/10.1007/s00415-022-11186-9

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  • DOI: https://doi.org/10.1007/s00415-022-11186-9

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