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PET Scanning Reveals Neurodegenerative Condition in Retired NFL Players

A version of this post first appeared in issue 14 of The Neurotransmitter

Junior Seau was one of the most decorated and beloved players in the National Football League (NFL) over an iconic professional career that spanned twenty seasons.  As a linebacker, a bruising defensive position tasked with tackling offensive ball carriers, Seau’s honors included twelve Pro Bowl selections, the NFL’s 1994 Man of the Year Award, and being named to the NFL 1990s All-Decade Team.  He developed a reputation for his ferocious play and passionate on-field leadership, often playing through injury and performing a distinctive fist-pumping dance after big plays [1].  Most would agree that Seau was a wonderful representative of the NFL before retiring in January 2010.

On May 2, 2012, at the age of 43, Junior Seau committed suicide by a self-inflicted gunshot wound to the chest.  His ex-wife reported that he had suffered from depression and insomnia in the last years of his life [2].  Suspecting that brain damage related to his long playing career contributed to his suicide, Seau’s family donated his brain tissue to the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH) for analysis.  On January 10, 2013, his family announced that NIH neuroscientists had definitively concluded that Seau suffered from chronic traumatic encephalopathy (CTE) [3], a degenerative neurological condition associated with concussion-related brain injury.

Seau’s post-mortem CTE diagnosis is one of several high profile cases that have brought recent media attention to a disturbing trend among retired professional football players.  Studies of former NFL players reveal a persistently higher rate of personality and mood disorders (e.g. major depression), mild cognitive impairment (MCI), and severe dementia compared to the general population.  In fact, retired NFL players sustaining three or more concussions during their careers may be three times more likely to be diagnosed with depression and five times more likely to be diagnosed with MCI later in life [4, 5].  Dozens of similar cases in former athletes who had suffered repetitive brain injuries are linked to CTE after death [6, 7].

CTE manifests as a steady deterioration in mood, personality, motor function, and cognition.  It is confirmed by a variety of findings at autopsy, particularly the widespread accumulation of phosphorylated tau protein tangles (similar to Alzheimer’s disease), axon damage, inflammation, and other brain abnormalities, including neuronal loss [6, 7].  Clearly, CTE can be a devastating consequence of repeated traumatic brain injury, and it is quite alarming that so many people are at risk due to the popularity of contact sports [8].  That retired NFL players are disproportionately more at risk for CTE should be cause for further unease among current players and league officials.  After all, American football is not merely a contact sport, according to legendary coach Vince Lombardi—it’s a collision sport.

Despite the risk for CTE among former athletes, there is no established method for its early detection.  All cases of CTE are currently diagnosed at autopsy.  However, in a clinical research article from the February 2013 issue of The American Journal of Geriatric Psychiatry, Dr. Gary W. Small and his UCLA colleagues describe a promising method for the non-invasive early detection of CTE and similar brain pathologies [9].

Dr. Small’s group previously invented a new tracer ligand for use in positron emission tomography (PET) that is capable of detecting tau tangle deposits in living brains, and can track and predict cognitive decline in people without dementia [10, 11].  A PET scanner detects the energy released by the decay of a special radioactive isotope (called a tracer) that is injected into the bloodstream and selectively binds to a tissue of interest.  The energy released by the bound tracer is then rendered into an image and color-coded for signal intensity.  In their latest study, Dr. Small’s research team applied this PET imaging technique to the brains of five living, retired NFL players with a history of cognitive or mood symptoms.

The former players, ranging in age from 45 to 73 and having sustained between one and twenty concussions during their playing careers, completed a battery of neuropsychological tests prior to PET scanning.  The tests revealed that the players indeed have significantly higher depression scores than control subjects, as well as a trend toward lower global cognitive ability.  These results closely reflect the players’ clinical presentation, as three were diagnosed with MCI, and another with dementia.  All exhibited symptoms of major depression.

More distressing, however, are the PET scans of the players’ brains: all had very high tracer signal intensity compared to controls that was especially concentrated in the thalamus, midbrain and amygdala, indicating large tau deposits in these regions (see Figure 1).  These binding patterns are consistent with the tau build-up observed in autopsy studies of CTE [6].  Perhaps the most striking feature of the study is the illustration of a relationship between PET signal intensity and the number of concussions each player sustained throughout his career (Figure 2).  Although none of the correlations reached statistical significance due to the small sample size of players tested, the plots below show a clear trend toward an increase in tracer binding with more concussions suffered.

This study may have a considerable impact in medicine and sports.  The PET tracer developed by Dr. Small’s team could facilitate the early detection of trauma-related brain diseases like CTE.  As the authors note, the early detection of this condition is a crucial first step toward the development of medical interventions that may hinder the onset or progression of symptoms.  No such early detection method is currently in practice.  This study should also help raise further awareness of the substantial long-term consequences of traumatic brain injuries in many at-risk athletes.  The NFL is now placing a much greater emphasis on player safety [12], having recently adopted new playing rules, medical guidelines and equipment standards to reduce the health risks of the game.  Researchers at Wake Forest University and Virginia Tech are aiding this initiative by conducting research on football helmets to reduce the number of concussions suffered [13].  The effectiveness of these measures remains to be seen, but the goal remains that at the end of their careers, players can truly leave all of the game on the field.


Figure 1 – Coronal and transaxial PET scans of retired NFL players show extremely high signals in cortical and subcortical brain regions compared to the control subject [9].


Figure 2 – Plots showing PET tracer binding according to number of concussions sustained suggest a positive relationship between greater number of concussions and higher PET tracer signal in several brain regions [9].


[1] http://www.utsandiego.com/news/2012/may/02/chargers-greats-feats-on-field-and-off-spoke-for/?print&page=all

[2] http://usatoday30.usatoday.com/sports/football/story/2012-05-31/Junior-Seau-suicide-last-days-sleep-issues/55316506/1

[3] http://abcnews.go.com/US/junior-seau-diagnosed-brain-disease-caused-hits-head/story?id=18171785&singlePage=true

[4] Guskiewicz KM, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery, 2005; 57:719-726.

[5] Guskiewicz KM, et al. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc, 2007; 39:903-909.

[6] McKee AC, et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy following repetitive head injury. J Neuropathol Exp Neurol, 2009; 68:709-735.

[7] McKee AC, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain, 2013; 136:43-64.

[8] Centers for Disease Control and Prevention: National Center for Injury Prevention and Control. Non-fatal traumatic brain injuries from sports and recreation activities—United States, 2001-2005. MMWR Weekly, 2007; 56(29):733-737.

[9] Small GW, et al. PET Scanning of Brain Tau in Retired National Football League Players: Preliminary Findings. Am J Geriatr Psychiatry, 2013; 21(2):138-144.

[10] Shoghi-Jadid K, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer’s disease. Am J Geriatr Psychiatry, 2002; 10:24-35.

[11] Small GW, et al. PET of brain amyloid and tau predicts and tracks cognitive decline in people without dementia. Arch Neurol, 2012; 69:215-222.

[12] Cf. http://www.nflevolution.com/

[13] http://www.news-medical.net/news/20130130/Wake-Forest-expands-football-helmet-research-to-reduce-sports-concussion-risks.aspx