Numerous studies have reported that sports-related concussions and traumatic injuries occur as a result of contact sports at all levels. Football players ranging from high school to professional are at particular risk. The Centers for Disease Control and Prevention (CDC) estimates that millions of these injuries occur each year. UCLA researchers note that despite the devastating consequences of traumatic brain injury and the large number of athletes playing contact sports who are at risk, no method has been developed for early detection or tracking of the brain pathology associated with these injuries. Therefore, they have developed a brain-imaging technique that can detect brain pathology at an early stage. In addition, to providing a diagnostic tool for traumatic brain injury, their research may lead to new diagnostic and treatment methods for Alzheimer’s disease. They reported their findings online on January 22 in the American Journal of Geriatric Psychiatry.
Previous reports and studies have shown that professional athletes in contact sports who are exposed to repetitive mild traumatic brain injuries may develop ongoing impairment such as chronic traumatic encephalopathy (CTE), a degenerative condition caused by a buildup of tau protein. CTE has been associated with memory loss, confusion, progressive dementia, depression, suicidal behavior, personality changes, abnormal gait and tremors. Researchers at the Semel Institute for Neuroscience and Human Behavior at UCLA have reported that for the first time they have used a brain-imaging tool to identify the abnormal tau proteins associated with this type of repetitive injury in five retired National Football League players who are still living. Previously, confirmation of the presence of this protein, which is also associated with Alzheimer’s disease, could only be established by an autopsy.
“Early detection of tau proteins may help us to understand what is happening sooner in the brains of these injured athletes,” noted lead study author Dr. Gary Small, UCLA’s Parlow–Solomon Professor on Aging and a professor of psychiatry and biobehavioral sciences at the Semel Institute. He added, “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.”
Dr. Small notes that the findings of their small study indicated that larger follow-up studies are needed to determine the impact and usefulness of detecting these tau proteins early. Beyond contact sports, many other individuals are at risk for mild traumatic brain injury such as military personnel and auto accident victims. Therefore, a means of testing what is happening in the brain during the early stages could potentially have a considerable impact on public health.
The investigators recruited five retired NFL players who were 45 years of age or older. Each had a history of one or more concussions and some were experiencing cognitive or mood symptoms. The players represented a range of positions, including linebacker, quarterback, guard, center and defensive lineman. “I hope that my participation in these kinds of studies will lead to a better understanding of the consequences of repeated head injury and new standards to protect players from sports concussions,” said Wayne Clark, a player in the study who had normal cognitive function.
The researchers used a brain-imaging tool they had developed previously for assessing neurological changes associated with Alzheimer’s disease. They employed a chemical marker they created called FDDNP, which binds to deposits of amyloid beta “plaques” and neurofibrillary tau “tangles,” which are the hallmarks of Alzheimer’s disease. After injecting the marker, they conducted a positron emission tomography (PET) scan, which provided a “window into the brain.” With this method, researchers are able to pinpoint where in the brain these abnormal proteins accumulate. The investigators compared the scans to those of healthy men of comparable age, education, body mass index, and family history of dementia.
The investigators found that compared to the healthy men, the NFL players had elevated levels of FDDNP in the amygdala and subcortical regions of the brain. These regions control learning, memory, behavior, emotions, and other mental and physical functions. Those players who had experienced a greater number of concussions were found to have 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,” explained study author Dr. Jorge R. Barrio, a professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.
In addition to the imaging studies, each of the players also received a standard clinical assessment to gauge their degree of depression (Hamilton Rating Scale for Depression, or HAM-D) and cognitive ability (Mini-Mental State Examination, or MMSE). The players had more depressive symptoms than the healthy men and generally scored lower on the MMSE test, demonstrating evidence of cognitive loss. Three players had mild cognitive impairment, one had dementia and another had normal cognitive function.
Dr. Barrio explained that elevated levels of FDDNP have been shown in studies to be associated with cognitive symptoms in normal aging, mild cognitive impairment and dementia. He added that the FDDNP signals appear to reflect a range of mental symptoms that have been observed in CTE cases. The FDDNP marker also binds to another abnormal brain protein called amyloid beta; however, previous autopsy studies have shown the amyloid plaques are observed in less than a third of CTE cases in retired football players, suggesting that the FDDNP signal in the players represents mostly tau deposits in the brain.
“Providing a non-invasive method for early detection is a critical first step in developing interventions to prevent symptom onset and progression in CTE,” noted Dr. Small. He added, “FDDNP is the only imaging marker currently available that can provide a measure of tau in living humans.” He noted that a recent study of more than 3,400 retired professional football players showed that they had a higher-than-average risk of dying from Alzheimer’s disease. Dr. Small’s team also is studying lifestyle interventions for delaying the onset of Alzheimer’s symptoms. His new book “The Alzheimer’s Prevention Program,” released in paperback this month, features the latest research on this topic and offers the public practical strategies for protecting brain health.