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

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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

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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/

  • 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 

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

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

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

    Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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].

  • 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 

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

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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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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