PET Imaging Reveals Damage From Head Injury in Living Athletes

Caroline Cassels

February 07, 2013

For the first time, researchers have been able to see the brain damage caused by repetitive head injury in living athletes, a finding that may help facilitate early identification and intervention in those suffering from trauma-related neurodegeneration.

Using PET imaging with FDDNP, a novel chemical tracer that binds to tau and amyloid in the brain, investigators at the University of California, Los Angeles, found that compared with control individuals, tau protein deposits were higher in all subcortical regions and in the amygdala in a group of 5 retired National Football League (NFL) players.

Tau proteins have previously been linked to chronic traumatic encephalopathy (CTE) as well as Alzheimer's disease (AD). A degenerative condition caused by the accumulation of tau in the brain, CTE has been associated with memory loss, confusion, progressive dementia, depression, suicidal behavior, personality changes, abnormal gait, and tremors.

However, until now, researchers were only able to confirm the presence of these proteins on autopsy.

"Early detection of tau proteins may help us to understand what is happening sooner in the brains of these injured athletes. Our findings may also guide us in developing strategies and interventions to protect those with early symptoms, rather than try to repair damage once it becomes extensive," principal investigator Gary Small, MD, said in a statement.

The study was published online January 22 in the American Journal of Geriatric Psychiatry.

Common Occurrence

With an estimated incidence of 1.6 to 3.8 million, sports-related repetitive mild traumatic brain injury due to contact sports are common.

According to the authors, research has shown that retired contact-sport athletes such as NFL players show higher rates of personality, behavioral, and mood disturbances, mild cognitive impairment, and dementia compared with control individuals.

In addition, there appears to be a dose-dependent effect. The investigators note that research in NFL players has shown that those with 3 or more reported concussions during their career were 3 times more likely to be diagnosed with depression and 5 times more likely to be diagnosed with mild cognitive impairment (MCI).

To determine whether brain tau deposits can be detected in living athletes using FDDNP-PET, potentially paving the way for early detection and intervention, the investigators conducted a study in 5 former NFL players who ranged in age from 45 to 73 years and who had a history of 1 or more concussions and cognitive or mood symptoms.

The players represented a range of positions, including linebacker, quarterback, guard, center, and defensive lineman.

Study participants underwent neuropsychiatric evaluations with the Hamilton Rating Scale for Depression and the Mini–Mental State Examination (MMSE) and underwent FDDNP-PET. PET signals in subcortical and cortical regions of the brain were then compared with those of 5 matched control participants.

Critical First Step

Results showed that the players had more depressive symptoms than the control participants and generally had lower MMSE scores, suggesting evidence of cognitive decline.

Three players had MCI, 1 had dementia, and 1 was cognitively normal.

The investigators found that FDDNP signals were higher in players compared with control participants in all subcortical regions and the amygdala areas that produce tau deposits following trauma. They also found that players who had experienced a greater number of concussions had higher FDDNP levels.

"The FDDNP binding patterns in the players' scans were consistent with the tau deposit patterns that have been observed at autopsy in CTE cases," study author Jorge R. Barrio, PhD, said in a release.

The investigators note that although FDDNP also binds to beta amyloid, a hallmark of AD, previous research has shown that amyloid plaques are found in less than one third of CTE cases, suggesting that the FDDNP signal in the NFL players mainly represents tau deposits.

"Providing a noninvasive method for early detection is a critical first step in developing interventions to prevent symptom onset and progression in CTE," said Dr. Small. He added that FDDNP is the "only imaging marker currently available that can provide a measure of tau in living humans."

The researchers added that in 2000, direct and indirect costs of traumatic brain injury was approximately $77 billion in the United States alone.

"Given the large number of people at risk — not just athletes but military personnel, auto accident victims, and others — the potential public health impact is considerable."

Dr. Small and Dr. Barrio report that they are among the inventors of FDDNP-PET, that they have received royalties, and that they may receive royalties on future sales. Dr. Small reports having served as a consultant and/or having received lecture fees from Janssen, Lilly, Novartis, and Pfizer. Dr. Barrio reports having served as a consultant and having received lecture fees from Nihon Medi-Physics Co, Bristol-Meyer Squibb, PETNET Pharmaceuticals, and Siemens. The other study authors have disclosed no relevant financial relationships.

Am J Geriatr Psychiatry. 2013;21:138-144. Full article