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CC BY-NC-ND 4.0 · Indian Journal of Neurotrauma 2022; 19(02): 063-068
DOI: 10.1055/s-0041-1725571
Review Article

Examining the Relationship between Concussion and Neurodegenerative Disorders: A Review on Amyotrophic Lateral Sclerosis and Alzheimer’s Disease

Edward Poluyi
1   Department of Clinical Neuroscience, University of Roehampton, London, United Kingdom
,
Eghosa Morgan
2   Department of Neurosurgery, Irrua Specialist Teaching Hospital, Irrua, Nigeria
,
Charles Poluyi
3   MPH Program, University of Buffalo, New York, United States
,
Chibuikem Ikwuegbuenyi 
4   Department of Surgery, Lagos University Teaching Hospital, Lagos, Nigeria
,
Grace Imaguezegie
4   Department of Surgery, Lagos University Teaching Hospital, Lagos, Nigeria
› Author Affiliations Funding None.
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Abstract

Background Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them.

Objectives This review will discuss the available literatures linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD).

Materials and Methods Given the complexity of this subject, a realist review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic.

Results Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Conclusion mTBI constitutes majority of brain injuries. However, studies have focused mostly on moderate-to-severe TBI as highlighted above with inconclusive and paucity of studies linking concussion and neurodegenerative disorders. Although, it is highly probable that repetitive concussion (mTBI) and subconcussive head injuries may be risk factors for ALS) and AD from this review. It will be imperative therefore to conduct more research with a focus on mTBI and its association with ALS and AD.

Keywords

mild traumatic brain injury - Alzheimer’s disease - neurodegeneration - amyotrophic lateral sclerosis (ALS)


Publication History

Article published online:
23 February 2021

© 2021. Neurotrauma Society of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Steven P Broglio, James T. Eckner, Henry L Paulson JSK. Cognitive decline and aging: the role of concussive and subconcussive impacts. Exerc Sport Sci Rev 2012;40(3):138–144
    PubMed
  • 2 Tagge CA, Fisher AM, Minaeva OV. et al Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model. Brain 2018; 141 (02) 422-458
    CrossrefPubMedGoogle Scholar
  • 3 Steenerson K, Starling AJ. Pathophysiology of sports-related concussion. Neurol Clin 2017; 35 (03) 403-408
    CrossrefPubMedGoogle Scholar
  • 4 LoBue C, Cullum CM, Didehbani N. et al Neurodegenerative dementias after traumatic brain injury. J Neuropsychiatry Clin Neurosci 2018; 30 (01) 7-13
    CrossrefPubMedGoogle Scholar
  • 5 Oliver JM, Anzalone AJ, Turner SM. Protection before impact: the potential neuroprotective role of nutritional supplementation in sports-related head trauma. Sports Med 2018; 48 (Suppl. 01) 39-52
    CrossrefPubMedGoogle Scholar
  • 6 Sundman MH, Hall EE, Chen N-K. Examining the relationship between head trauma and neurodegenerative disease: a review of epidemiology, pathology and neuroimaging techniques. J Alzheimers Dis Parkinsonism 2014; 4: 137
    PubMedGoogle Scholar
  • 7 Rosenman M, Gero J, Al-Chalabi A. et al Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology. Amyotroph Lateral Scler Front Degener 2018; 7 (04) 1-10
    PubMedGoogle Scholar
  • 8 Noble JM, Hesdorffer DC. Sport-related concussions: a review of epidemiology, challenges in diagnosis, and potential risk factors. Neuropsychol Rev 2013; 23 (04) 273-284
    CrossrefPubMedGoogle Scholar
  • 9 Mckee A. Military TBI. Alzheimers Dement J Alzheimers Assoc 2014; 10 (3 0) S242-S253
    PubMedGoogle Scholar
  • 10 Shin SS, Pathak S, Presson N. et al Detection of white matter injury in concussion using high-definition fiber tractography. Prog Neurol Surg 2014; 28: 86-93
    CrossrefPubMedGoogle Scholar
  • 11 McKee AC, Robinson ME. Military-related traumatic brain injury and neurodegeneration. Alzheimers Dement 2014; 10 (Suppl. 03) S242-S253
    PubMedGoogle Scholar
  • 12 Aging and Cognitive Decline as a Result of Concussive Impacts. Manuscript A, Decline C, Impacts S. 2013;40(3):138–14410.1097/JES.0b013e3182524273.Cognitive
    PubMed
  • 13 Moore RD, Lepine J, Ellemberg D. The independent influence of concussive and sub-concussive impacts on soccer players’ neurophysiological and neuropsychological function. Int J Psychophysiol 2017; 112: 22-30
    CrossrefPubMedGoogle Scholar
  • 14 Papa L. Potential blood-based biomarkers for concussion. Sports Med Arthrosc Rev 2016; 24 (03) 108-115
    CrossrefPubMedGoogle Scholar
  • 15 Ling H, Hardy J, Zetterberg H. Neurological consequences of traumatic brain injuries in sports. Mol td Neurosci 2015; 66 (Pt B) 114-122
    CrossrefPubMedGoogle Scholar
  • 16 Logsdon AF, Lucke-wold BP, Turner RC, Huber JD, Rosen CL, Simpkins JW. Role of microvascular disruption in brain damage from traumatic brain injury. Compr Physiol 2015;5(3):1147–1160
    PubMed
  • 17 Chen M, Song H, Cui J. et al Proteomic profiling of mouse brains exposed to blast-induced mild traumatic brain injury reveals changes in axonal proteins and phosphorylated tau. J Alzheimers Dis 2018; 66 (02) 751-773
    CrossrefPubMedGoogle Scholar
  • 18 Pupillo E, Messina P, Logroscino G. et al; EURALS Consortium. Trauma and amyotrophic lateral sclerosis: a case-control study from a population-based registry. Eur J Neurol 2012; 19 (12) 1509-1517
    CrossrefPubMedGoogle Scholar
  • 19 Broussard JI, Acion L, De Jesús-cortés H. et al Repeated mild traumatic brain injury produces neuroinflammation, anxiety-like behaviour and impaired spatial memory in mice. Brain Inj 32 (01) 113-122
    CrossrefPubMedGoogle Scholar
  • 20 DeKosky ST, Asken BM. Injury cascades in TBI-related neurodegeneration. Brain Inj 2017; 31 (09) 1177-1182
    CrossrefPubMedGoogle Scholar
  • 21 Mouzon BC, Bachmeier C, Ojo JO. et al Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury. Ann Clin Transl Neurol 2017; 5 (01) 64-80
    CrossrefPubMedGoogle Scholar
  • 22 Dashnaw ML, Petraglia AL, Bailes JE. The biophysics of head impact. Neurosurg Focus 2012; 33 (06) E5, 1-9
    PubMedGoogle Scholar
  • 23 Grant DA, Serpa R, Moattari CR. et al Repeat mild traumatic brain injury in adolescent rats increases subsequentβ-amyloid pathogenesis. J Neurotrauma 2018; 35 (01) 94-104
    CrossrefPubMedGoogle Scholar
  • 24 Al-Chalabi A, Hardiman O, Kiernan MC, Chiò A, Rix-Brooks B, van den Berg LH. Amyotrophic lateral sclerosis: moving towards a new classification system. Lancet Neurol 2016; 15 (11) 1182-1194
    CrossrefPubMedGoogle Scholar
  • 25 Fang T, Al Khleifat A, Stahl DR. et al; Uk-Mnd LicalS. Comparison of the King’s and MiToS staging systems for ALS. Amyotroph Lateral Scler Frontotemporal Degener 2017; 18 (3-4) 227-232
    CrossrefPubMedGoogle Scholar
  • 26 Brain V. Defense and Veterans brain injury centre information paper on Amyotrophic Lateral Sclerosis and Traumatic Brain Injury issue. Info Pap 2018;1:2014–2017
    PubMed
  • 27 Cykowski MD, Powell SZ, Peterson LE. et al Clinical significance of TDP-43 neuropathology in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2017; 76 (05) 402-413
    CrossrefPubMedGoogle Scholar
  • 28 Tiryaki E, Horak HA. ALS and other motor neuron diseases. 2014; 20 (05) 1185-1207
    PubMedGoogle Scholar
  • 29 Armon C, Nelson LM. Is head trauma a risk factor for amyotrophic lateral sclerosis? An evidence based review. Amyotroph Lateral Scler 2012; 13 (04) 351-356
    CrossrefPubMedGoogle Scholar
  • 30 Peters TL, Fang F, Weibull CE, Sandler DP, Kamel F, Ye W. Severe head injury and amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14 (04) 267-272
    CrossrefPubMedGoogle Scholar
  • 31 Rosenman M, Gero J. Evolving designs by generating useful complex gene structures. Evol Comput 1999; 166 (07) 345-364
    PubMedGoogle Scholar
  • 32 Wright DK, Liu S, van der Poel C. et al Traumatic brain injury results in cellular, structural and functional changes resembling motor neuron disease. Cereb Cortex 2017; 27 (09) 4503-4515
    PubMedGoogle Scholar
  • 33 Fakhran S, Alhilali L. Neurodegenerative changes after mild traumatic brain injury. Prog Neurol Surg 2014; 28: 234-242
    CrossrefPubMedGoogle Scholar
  • 34 Nelson EE, Guyer AE. The development of the ventral prefrontal cortex and social flexibility. Dev Cogn Neurosci 2011; 1 (03) 233-245
    CrossrefPubMedGoogle Scholar
  • 35 Hayes JP, Logue MW, Sadeh N. et al Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer’s disease. Brain 2017; 140 (03) 813-825
    PubMedGoogle Scholar
  • 36 Tateno A, Sakayori T, Takizawa Y, Yamamoto K, Minagawa K, Okubo Y. A case of Alzheimer’s disease following mild traumatic brain injury. Gen Hosp Psychiatry 2015; 37 (01) 97.e7-97.e9
    CrossrefPubMedGoogle Scholar