PET depicts concussion-related brain pathology in ex-NFL players

Using a chemical marker that binds to abnormal tau proteins, researchers at the University of California, Los Angeles (UCLA), for the first time have imaged the brain pathology associated with sports-related concussions in patients who are still alive.

The preliminary findings of the small study, which used PET scans to image five retired National Football League players, were published online Jan. 22 in the American Journal of Geriatric Psychiatry.

“Despite the devastating consequences of [traumatic brain injuires] TBIs due to contact sports and the large number of people at risk, no method for early detection of brain pathology has yet been established,” wrote Gary Small, MD, of UCLA, and colleagues.

Previous studies have shown that professional athletes in contact sports who are exposed to repetitive mild TBIs may develop chronic traumatic encephalopathy (CTE), a degenerative condition caused by a build-up of tau protein. CTE has been associated with memory loss, confusion, progressive dementia, suicidal behavior and other conditions, but confirmation of the presence of this protein could previously only be established by an autopsy.

The researchers’ technique utilized intravenous injections of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile, or FDDNP. Small and his colleagues at UCLA had previously developed the imaging agent for assessing neurological changes associated with Alzheimer’s disease (AD).

The five former football players with histories of mood and cognitive symptoms received neuropsychiatric evaluations and were matched with five healthy men of comparable age, education, body mass index and family history of dementia. All subjects underwent FDDNP-PET imaging focused on signals in the amygdala and subcortical regions of the brain—regions that control learning, memory, behavior, emotions and other functions.

FDDNP signals were higher in players compared with the controls in all subcortical regions and the amygdala areas that produce tau deposits following trauma, reported Small and colleagues. The players who had experienced a greater number of concussions were found to have higher FDDNP levels.

FDDNP also binds to amyloid beta plaques, but previous autopsies have shown that these plaques are observed in less than one-third of CTE cases in retired players, meaning the FDDNP signal likely represents tau deposits.

“The pattern of higher FDDNP binding values in players with a greater number of concussions suggests a link between the players’ history of head injury and FDDNP binding,” wrote the authors. “Moreover, these binding patterns (high subcortical and low cortical binding except for the amygdala) are consistent with tau deposition patterns observed in autopsy studies of CTE and differ from those observed in patients with cognitive and mood symptoms without prior head trauma, who mainly present with increased cortical FDDNP binding.”

Standard clinical assessments found the players had more depressive symptoms than the healthy men, and generally scored lower on the Mini-Mental State Examination test of cognitive ability. Three players had mild cognitive impairment, one had dementia and another had normal cognitive function.

The findings suggest that FDDNP-PET could be used for early identification of trauma-related neurodegeneration. “Early recognition and identification of those at high risk would allow clinicians to develop strategies and interventions to protect those with early symptoms rather than attempt to repair damage once it becomes extensive,” wrote the authors.