Advertisement

Neuropsychology Review

, Volume 23, Issue 4, pp 350–360 | Cite as

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

  • Stella KarantzoulisEmail author
  • Christopher Randolph
Review

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.

Keywords

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

Notes

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.

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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Corsellis, J. A., Bruton, C. J., & Freeman-Browne, D. (1973). The aftermath of boxing. Psychological Medicine, 3(3), 270–303.PubMedCrossRefGoogle 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.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Critchley, M. (1957). Medical aspects of boxing, particularly from a neurological standpoint. British Medical Journal, 1(5015), 357–362.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefGoogle 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.PubMedGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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].Google Scholar
  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.CrossRefGoogle Scholar
  46. Roberts, A. H. (1969). Brain damage in boxers: a study of the prevalence of traumatic encephalopathy among ex-professional boxers. London: Pitman.Google Scholar
  47. Roberts, G. W., Allsop, D., & Bruton, C. (1990). The occult aftermath of boxing. Journal of Neurology, Neurosurgery, and Psychiatry, 53(5), 373–378.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefPubMedCentralGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of NeurologyNYU School of MedicineNew YorkUSA
  2. 2.Department of NeurologyLoyola University Medical CenterMaywoodUSA
  3. 3.New York University Langone Medical UniversityNew YorkUSA

Personalised recommendations