. Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired association football (soccer) players. Acta Neuropathol. 2017 Mar;133(3):337-352. Epub 2017 Feb 15 PubMed.


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  1. This is an important clinicopathological case study involving a small cohort of demented subjects who were exposed to repetitive head impacts (RHI) through soccer participation for a prolonged period of time (average 26 years). The report greatly enhances the existing literature, as it is the largest postmortem series of soccer players ever reported. There are also several clinical and pathological features that are worth highlighting. First, all six players were initially diagnosed clinically and pathologically as having Alzheimer’s disease (AD), although the pathological diagnosis was changed to include CTE in four of the six after reexamination. This indicates that there is a critical need to go back and re-evaluate existing brain bank series for the presence of CTE using the recently defined NINDS criteria (McKee et al., 2016). Although this has been done by several groups (Bieniek et al., 2015; Ling et al., 2015; and Noy et al., 2016), the current study further emphasizes that CTE can masquerade as AD, pathologically and clinically, and is likely contaminating clinical trials and basic research studies in AD.

    Another notable feature is that the soccer players with CTE had only one documented concussion, highlighting again that CTE is associated with prolonged exposure to mild RHI that are frequently clinically silent and do not rise to the level of a symptomatic concussion.

    In addition, all six players had evidence of AD and previous traumatic injury (fenestrations of the septum pellucidum and one with cavum septum), including the two that did not meet NINDS criteria for CTE. This raises the question of whether prolonged exposure to RHI also accelerates or enhances the development of AD. Recently, the late-life effects of single traumatic brain injury (TBI) with loss of consciousness (LOC) were analyzed in 7,130 subjects from three large participant studies and found that TBI with LOC was not associated with cognitive impairment, dementia, clinical AD, or AD neuropathology, but was associated with Parkinson’s disease, parkinsonism, Lewy bodies and microinfarcts (Crane et al., 2016). Although this study suggests that single TBI with LOC is not associated with AD, it does not provide insight into the role of RHI in AD or how the co-existence of CTE might modify that relationship. Future studies are needed to evaluate how exposure to RHI and the presence of CTE impact the development of AD.


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    . Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank. Acta Neuropathol. 2015 Dec;130(6):877-89. Epub 2015 Oct 30 PubMed.

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    View all comments by Ann McKee
  2. This is an important and valuable addition to the literature on the potential link between chronic, repetitive head injury (with heading in football being used as the model) and the risk of the later development of chronic traumatic encephalopathy.

    Despite the limitations of the study—namely no control group and no denominator (the study recruited consecutive ex-footballers who attended a memory clinic in one region over 30 years. We are left to speculate as to how many footballers did not experience memory decline or how many did not have their past sporting history explored in clinic)—the extent of the findings, particularly at postmortem, make this a very valuable study.

    Of the six players who underwent a postmortem, four had confirmed CTE and two had changes suggestive of CTE. The 100 percent prevalence of septal fenestration is perhaps the most striking pathological finding of all. It suggests that chronic low-level trauma was responsible for this change, particularly if the self-reported low prevalence of concussive injury in this group is accurate. The background population prevalence of just 6 percent makes this finding even more striking. Additionally, only six of the 14 participants reported a concussion during their career, however, retrospective accounts of head injury particularly are prone to recall bias and should be interpreted with caution.

    It is also worth noting that all six patients who underwent postmortem had experienced significant personality changes as an early clinical feature, typically an increase in aggression. This supports previous studies in boxers and American football players and suggests that this may be a robust clinical biomarker of CTE. Another noteworthy clinical finding is the age of onset, with five of the 14 participants presenting with symptoms under the age of 60. This may reflect a more extensive exploration of past history (including sporting history) in patients who present young, and I am cautious about over-interpretation without knowing how many people in the population were also exposed to similar levels of chronic low-level head trauma. Nevertheless, these were unusually young patients experiencing significant clinical problems and the pathological findings support the likelihood that heading a football may have contributed to their early presentation.

    The study does not address what factors place footballers at additional risk or those that may be protective. For every Jeff Astle there may be a Stanley Matthews, who died at 85 cognitively intact. The study acknowledges the desirability of having background genetic information—particularly ApoE E4 status—in these studies and also the difficulty of knowing the threshold for causing damage as well as mentioning that the change in a football design and weight may or may not have changed the level of risk. All 14 participants had used the old, 480g football at some point in their career. 

    The authors call for larger, prospective studies using a variety of imaging and other investigative techniques and certainly this would be desirable. However, I would like to see more made of the changes in personality in ex-players if this is indeed an early clinical biomarker for CTE. The alternative is to conduct an “ideal” prospective study of current players with accurate measures of trauma exposure and prospective follow-up. The results of such a study may not be conclusive for decades.

    Regardless of the limitations of this study, the findings raise an alarm for all sports and activities that involve low-level head trauma and should encourage further measures to mitigate this risk. 

    View all comments by Simon Vann Jones
  3. This study by Ling et al. increases the number of football (soccer) cases in the literature with some element of CTE pathology. Although the numbers still remain small, the authors indicate that four of six cases with CTE pathology is a much higher percentage than what may be expected in an elderly population, thereby supporting the hypothesis that CTE pathology in football players may be related to the prior history of heading the ball and/or player collisions. Having two of the six without CTE pathology is also an interesting finding because it suggests that some individuals may be more susceptible or resilient to forming CTE pathology than others. As with most of the prior football (soccer) CTE cases, the research subjects in the study had mixed pathologies (AD, TDP43, CTE), and this supports the concept of possible synergy with the aging process and/or other neurodegenerative diseases.

    Overall, the authors point out limitations to the study, including small size and lack of some other detailed metrics, however, they also suggest that the prospective accumulation of histories and regular outpatient surveillance reduced selection and recall bias. Larger longitudinal prospective studies on football (soccer) players are needed to understand the scope of CTE pathology and traumatic encephalopathy syndrome in this patient population. We are hopeful that novel biomarkers (CSF, PET imaging, etc) will soon assist with diagnosis and also provide much-needed insight into how pathology/biomarkers may correlate with clinical symptoms. 

    View all comments by Chad Hales

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