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Modern Chronic Traumatic Encephalopathy in Retired Athletes: What is the Evidence?

Abstract

It has been theorized that a career in contact sports may be associated with long-term neurodegenerative changes. This idea dates as far back as the 1920s, was initially reported in boxers, colloquially termed ‘punch drunk,’ later more formally termed dementia pugilistica (DP), and now coined chronic traumatic encephalopathy (CTE). Despite considerable ongoing interest on this topic, there is so far only limited evidence showing an association between sport-related concussion (SRC) and increased risk for late-life cognitive and neuropsychiatric impairment, with no causality or risk factors yet determined. The modern CTE description is nevertheless proposed as a unique tauopathy with characteristic pathological stages occurring in retired athletes who have experienced previous repetitive brain trauma. This review highlights the principal issues that so far preclude firm conclusions about the association of athletic head trauma and neurodegenerative diseases of any type. We consider alternative interpretations that may contribute to the clinical progressive neurological findings in some athletes and recommend carefully-controlled epidemiological work to overcome current limitations in this area of research and stimulate future research.

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References

  1. Baron, S. L., Hein, M. J., Lehman, E., & Gersic, C. M. (2012). Body mass index, playing position, race, and the cardiovascular mortality of retired professional football players. American Journal of Cardiology, 109(6), 889–896. doi:10.1016/j.amjcard.2011.10.050.

    PubMed  Article  Google Scholar 

  2. Bennett, D. A., Schneider, J. A., Wilson, R. S., Bienias, J. L., & Arnold, S. E. (2004). Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Archives of Neurology, 61(3), 378–384. doi:10.1001/archneur.61.3.378.

    PubMed  Article  Google Scholar 

  3. Bennett, D. A., Schneider, J. A., Arvanitakis, Z., Kelly, J. F., Aggarwal, N. T., Shah, R. C., et al. (2006). Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology, 66(12), 1837–1844. doi:10.1212/01.wnl.0000219668.47116.e6.

    PubMed  Article  CAS  Google Scholar 

  4. Clausen, H., McCrory, P., & Anderson, V. (2005). The risk of chronic traumatic brain injury in professional boxing: change in exposure variables over the past century. British Journal of Sports Medicine, 39(9), 661–664. doi:10.1136/bjsm.2004.017046. discussion 664.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  5. Corsellis, J. A., Bruton, C. J., & Freeman-Browne, D. (1973). The aftermath of boxing. Psychological Medicine, 3(3), 270–303.

    PubMed  Article  CAS  Google Scholar 

  6. Costanza, A., Weber, K., Gandy, S., Bouras, C., Hof, P. R., Giannakopoulos, P., et al. (2011). Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates. Neuropathology and Applied Neurobiology, 37(6), 570–584. doi:10.1111/j.1365-2990.2011.01186.x.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  7. Critchley, M. (1957). Medical aspects of boxing, particularly from a neurological standpoint. British Medical Journal, 1(5015), 357–362.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  8. Fleminger, S., Oliver, D. L., Lovestone, S., Rabe-Hesketh, S., & Giora, A. (2003). Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication. Journal of Neurology, Neurosurgery, and Psychiatry, 74(7), 857–862.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  9. Gao, L., Tian, S., Gao, H., & Xu, Y. (2013). Hypoxia increases Abeta-induced Tau phosphorylation by Calpain and promotes behavioral consequences in AD transgenic mice. Journal of Molecular Neuroscience, 51(1), 138–147. doi:10.1007/s12031-013-9966-y.

    PubMed  Article  CAS  Google Scholar 

  10. Gardner, A., Iverson, G. L., & McCrory, P. (2013). Chronic traumatic encephalopathy in sport: a systematic review. British Journal of Sports Medicine. doi:10.1136/bjsports-2013-092646.

    Google Scholar 

  11. Gavett, B. E., Cantu, R. C., Shenton, M., Lin, A. P., Nowinski, C. J., McKee, A. C., et al. (2011a). Clinical appraisal of chronic traumatic encephalopathy: current perspectives and future directions. Current Opinion in Neurology, 24(6), 525–531. doi:10.1097/WCO.0b013e32834cd477.

    PubMed  Article  Google Scholar 

  12. Gavett, B. E., Stern, R. A., & McKee, A. C. (2011b). Chronic traumatic encephalopathy: a potential late effect of sport-related concussive and subconcussive head trauma. Clinics in Sports Medicine, 30(1), 179–188. doi:10.1016/j.csm.2010.09.007. xi.

    PubMed  Article  PubMed Central  Google Scholar 

  13. Geddes, J. F., Vowles, G. H., Robinson, S. F., & Sutcliffe, J. C. (1996). Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathology and Applied Neurobiology, 22(1), 12–16.

    PubMed  Article  CAS  Google Scholar 

  14. Geddes, J. F., Vowles, G. H., Nicoll, J. A., & Revesz, T. (1999). Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathologica, 98(2), 171–178.

    PubMed  Article  CAS  Google Scholar 

  15. Gelber, R. P., Launer, L. J., & White, L. R. (2012). The Honolulu-Asia aging study: epidemiologic and neuropathologic research on cognitive impairment. Current Alzheimer Research, 9(6), 664–672.

    PubMed  Article  CAS  Google Scholar 

  16. Genis, L., Chen, Y., Shohami, E., & Michaelson, D. M. (2000). Tau hyperphosphorylation in apolipoprotein E-deficient and control mice after closed head injury. Journal of Neuroscience Research, 60(4), 559–564.

    PubMed  Article  CAS  Google Scholar 

  17. Guskiewicz, K. M., Marshall, S. W., Bailes, J., McCrea, M., Cantu, R. C., Randolph, C., et al. (2005). Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery, 57(4), 719–726. discussion 719–726.

    PubMed  Article  Google Scholar 

  18. Hart, J., Jr., Kraut, M. A., Womack, K. B., Strain, J., Didehbani, N., Bartz, E., et al. (2013). Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. JAMA Neurology, 70(3), 326–335. doi:10.1001/2013.jamaneurol.340.

    PubMed  Article  Google Scholar 

  19. Hazrati, L. N., Tartaglia, M. C., Diamandis, P., Davis, K. D., Green, R. E., Wennberg, R., et al. (2013). Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology. Frontiers in Human Neuroscience, 7, 222. doi:10.3389/fnhum.2013.00222.

    PubMed  Article  PubMed Central  Google Scholar 

  20. Hohler, B. (2009). Major breakthrough in concussion crisis: researchers find signs of degenerative brain disease in an 18-year-old high school football player. Accessed 21 Jan 2010. Retrieved from www.boston.com/sports/other_sports/articles/2009/01/27/major_breakthrough_in_concussion_crisis/

  21. Iverson, G. L. (2013). Chronic traumatic encephalopathy and risk of suicide in former athletes. British Journal of Sports Medicine. doi:10.1136/bjsports-2013-092935.

    Google Scholar 

  22. Jellinger, K. A. (2004). Head injury and dementia. Current Opinion in Neurology, 17(6), 719–723.

    PubMed  Article  Google Scholar 

  23. Jordan, B. D. (2013). The clinical spectrum of sport-related traumatic brain injury. Nature Reviews Neurology, 9(4), 222–230, doi:10.1038/nrneurol.2013.33.

    Google Scholar 

  24. Jordan, B. D., Relkin, N. R., Ravdin, L. D., Jacobs, A. R., Bennett, A., & Gandy, S. (1997). Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA, 278(2), 136–140.

    PubMed  Article  CAS  Google Scholar 

  25. Lee, C. W., Shih, Y. H., Wu, S. Y., Yang, T., Lin, C., & Kuo, Y. M. (2013). Hypoglycemia induces tau hyperphosphorylation. Current Alzheimer Research, 10(3), 298–308.

    PubMed  Article  CAS  Google Scholar 

  26. Lehman, E. J., Hein, M. J., Baron, S. L., & Gersic, C. M. (2012). Neurodegenerative causes of death among retired National Football League players. Neurology, 79(19), 1970–1974. doi:10.1212/WNL.0b013e31826daf50.

    PubMed  Article  Google Scholar 

  27. Loosemore, M., Knowles, C. H., & Whyte, G. P. (2007). Amateur boxing and risk of chronic traumatic brain injury: systematic review of observational studies. BMJ, 335(7624), 809. doi:10.1136/bmj.39342.690220.55.

    PubMed  Article  PubMed Central  Google Scholar 

  28. Lyketsos, C. G., Steinberg, M., Tschanz, J. T., Norton, M. C., Steffens, D. C., & Breitner, J. C. (2000). Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. The American Journal of Psychiatry, 157(5), 708–714.

    PubMed  Article  CAS  Google Scholar 

  29. McCrea, M., Iverson, G. L., McAllister, T. W., Hammeke, T. A., Powell, M. R., Barr, W. B., et al. (2009). An integrated review of recovery after mild traumatic brain injury (MTBI): implications for clinical management. Clinical Neuropsychology, 23(8), 1368–1390. doi:10.1080/13854040903074652.

    Article  Google Scholar 

  30. McKee, A. C., Cantu, R. C., Nowinski, C. J., Hedley-Whyte, E. T., Gavett, B. E., Budson, A. E., et al. (2009). Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. Journal of Neuropathology and Experimental Neurology, 68(7), 709–735. doi:10.1097/NEN.0b013e3181a9d503.

    PubMed  Article  PubMed Central  Google Scholar 

  31. McKee, A. C., Gavett, B. E., Stern, R. A., Nowinski, C. J., Cantu, R. C., Kowall, N. W., et al. (2010). TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. Journal of Neuropathology and Experimental Neurology, 69(9), 918–929. doi:10.1097/NEN.0b013e3181ee7d85.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  32. McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E., et al. (2013). The spectrum of disease in chronic traumatic encephalopathy. Brain, 136(Pt 1), 43–64. doi:10.1093/brain/aws307.

    PubMed  Article  Google Scholar 

  33. Mendez, M. F. (1995). The neuropsychiatric aspects of boxing. International Journal of Psychiatry in Medicine, 25(3), 249–262.

    Google Scholar 

  34. Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., et al. (2012). Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. Journal of Neuropathology and Experimental Neurology, 71(5), 362–381. doi:10.1097/NEN.0b013e31825018f7.

    PubMed  Article  PubMed Central  Google Scholar 

  35. Omalu, B. I., DeKosky, S. T., Minster, R. L., Kamboh, M. I., Hamilton, R. L., & Wecht, C. H. (2005). Chronic traumatic encephalopathy in a National Football League player. Neurosurgery, 57(1), 128–134. discussion 128–134.

    PubMed  Article  Google Scholar 

  36. Omalu, B. I., DeKosky, S. T., Hamilton, R. L., Minster, R. L., Kamboh, M. I., Shakir, A. M., et al. (2006). Chronic traumatic encephalopathy in a national football league player: part II. Neurosurgery, 59(5), 1086–1092. doi:10.1227/01.neu.0000245601.69451.27. discussion 1092–1083.

    PubMed  Google Scholar 

  37. Omalu, B. I., Fitzsimmons, R. P., Hammers, J., & Bailes, J. (2010a). Chronic traumatic encephalopathy in a professional American wrestler. Journal of Forensic Nursing, 6(3), 130–136. doi:10.1111/j.1939-3938.2010.01078.x.

    PubMed  Article  Google Scholar 

  38. Omalu, B. I., Hamilton, R. L., Kamboh, M. I., DeKosky, S. T., & Bailes, J. (2010b). Chronic traumatic encephalopathy (CTE) in a National Football League Player: Case report and emerging medicolegal practice questions. Journal of Forensic Nursing, 6(1), 40–46. doi:10.1111/j.1939-3938.2009.01064.x.

    PubMed  Article  Google Scholar 

  39. Omalu, B., Bailes, J., Hamilton, R. L., Kamboh, M. I., Hammers, J., Case, M., et al. (2011a). Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery, 69(1), 173–183. doi:10.1227/NEU.0b013e318212bc7b. discussion 183.

    PubMed  Article  Google Scholar 

  40. Omalu, B., Hammers, J. L., Bailes, J., Hamilton, R. L., Kamboh, M. I., Webster, G., et al. (2011b). Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. Neurosurgical Focus, 31(5), E3. doi:10.3171/2011.9.focus11178.

    PubMed  Article  Google Scholar 

  41. Plassman, B. L., Havlik, R. J., Steffens, D. C., Helms, M. J., Newman, T. N., Drosdick, D., et al. (2000). Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology, 55(8), 1158–1166.

    PubMed  Article  CAS  Google Scholar 

  42. Randolph, C., & Kirkwood, M. W. (2009). What are the real risks of sport-related concussion, and are they modifiable? Journal of International Neuropsychological Society, 15(4), 512–520. doi:10.1017/s135561770909064x.

    Article  Google Scholar 

  43. Randolph, C., Tierney, M. C., Mohr, E., & Chase, T. N. (1998). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. Journal of Clinical and Experimental Neuropsychology, 20(3), 310–319. doi:10.1076/jcen.20.3.310.823.

    PubMed  Article  CAS  Google Scholar 

  44. Randolph, C., Goldberg, M., & Morimoto, B. (2012). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in progressive supranuclear palsy: Baseline data from the Allon Therapeutics AL-108-231 multinational clinical trial. [Poster Presented at the Alzheimer's Association International Conference, Vancouver, Canada].

  45. Randolph, C., Karantzoulis, S., & Guskiewicz, K. (2013). Prevalence and characterization of mild cognitive impairment in retired national football league players. Journal of International Neuropsychological Society, 19(8), 873–880. doi:10.1017/s1355617713000805.

    Article  Google Scholar 

  46. Roberts, A. H. (1969). Brain damage in boxers: a study of the prevalence of traumatic encephalopathy among ex-professional boxers. London: Pitman.

  47. Roberts, G. W., Allsop, D., & Bruton, C. (1990). The occult aftermath of boxing. Journal of Neurology, Neurosurgery, and Psychiatry, 53(5), 373–378.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  48. Savica, R., Parisi, J. E., Wold, L. E., Josephs, K. A., & Ahlskog, J. E. (2012). High school football and risk of neurodegeneration: a community-based study. Mayo Clinic Proceedings, 87(4), 335–340. doi:10.1016/j.mayocp.2011.12.016.

    PubMed  Article  PubMed Central  Google Scholar 

  49. Stern, R. A., Daneshvar, D. H., Baugh, C. M., Seichepine, D. R., Montenigro, P. H., Riley, D. O., et al. (2013). Clinical presentation of chronic traumatic encephalopathy. Neurology, 81(13), 1122–1129. doi:10.1212/WNL.0b013e3182a55f7f.

    PubMed  Article  Google Scholar 

  50. Wen, Y., Yang, S. H., Liu, R., Perez, E. J., Brun-Zinkernagel, A. M., Koulen, P., et al. (2007). Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats. Biochimica et Biophysica Acta, 1772(4), 473–483. doi:10.1016/j.bbadis.2006.10.011.

    PubMed  Article  CAS  Google Scholar 

  51. Wright, A. D. (1965). Head injuries. In A. L. Bass, J. L. Blonstein, R. D. James, & J. P. Williams (Eds.), Medical aspects of boxing (p. 61). London: Pergamon Press.

    Google Scholar 

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Financial Disclosures

Portions of this research were presented at the annual meeting of Alzheimer's Association International Conference, Vancouver, Canada. Dr. Randolph is the author of the RBANS, and receives royalty payments from the publisher and copyright holder of the test, Pearson, Inc.

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Correspondence to Stella Karantzoulis.

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Karantzoulis, S., Randolph, C. Modern Chronic Traumatic Encephalopathy in Retired Athletes: What is the Evidence?. Neuropsychol Rev 23, 350–360 (2013). https://doi.org/10.1007/s11065-013-9243-4

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Keywords

  • Sport-related concussion
  • Chronic traumatic encephalopathy
  • Dementia pugilistica
  • Alzheimer’s disease
  • Tauopathies