Patients with chronic trauma-related brain disease may develop in two distinct ways, one involving mood and behavioral disorders and the other by cognitive impairment, according to a study that combined prospective and postmortem data.
Almost all of the 36 patients with chronic traumatic encephalopathy (CTE) had a combination of cognitive, mood, and behavioral disorders, and cognitive impairment was almost universal.
However, almost two-thirds of the patients developed mood and behavioral disturbances at a younger age and died at a younger age. The rest of the patients had predominately cognitive impairment, which had later onset and was associated with death at an older age, Robert A. Stern, PhD, of Boston University, and co-authors reported online in Neurology.
"At this point, CTE can be diagnosed only when someone passes away, postmortem," Stern told MedPage Today. "Because of that we can't begin to evaluate treatments or potential cures for the disease. What we're trying to do is establish what someone looks like when someone is alive."
"This is our first look at what the disease might look like in individuals who are still alive," he added. "Ultimately, we hope this will help us diagnose and eventually treat and cure people while they are still alive."
To date all neuropathologically confirmed cases of CTE have involved people with a history of repeated brain trauma, such as boxers, football players, and combat-experienced military personnel.
However, not all people exposed to repeated brain trauma develop CTE, suggesting other factors contribute to neuropathogenesis. The APOE e4 allele has been posited as a susceptibility factor for CTE, the authors noted.
Published descriptions of CTE have revealed a constellation of clinical features, including impaired cognition, behavior and mood disturbance, chronic headache, and motor and cerebellar dysfunction. Previous reports involving boxers suggested types of clinical presentation: behavior and mood disturbance associated with younger age, and primarily cognitive impairment with onset in older age.
To inform the search for better identification and treatment of CTE, Stern and colleagues identified 36 adult males with pathologically confirmed CTE at the Center for the Study of Traumatic Encephalopathy brain bank. All were athletes with no comorbid neurodegenerative or motor neuron disease. Investigators obtained retrospective medical histories of the 36 men from family members, who also described features of the clinical presentation.
Of the 36 men included in the study, 29 had been football players, including 22 who played professionally. The remaining members of the group consisted of three professional hockey players, one professional wrestler, and three boxers. Three of the 36 had been asymptomatic at the time of death.
In 11 of 33 symptomatic cases, initial signs and symptoms of CTE reflected impaired cognitive functioning, followed later by mood and behavioral disturbance. Of the remaining 22 patients, behavioral changes (described as explositivity, impulsivity, and violence) were the first signs of CTE in 13, and mood changes (such as depression and hopelessness) occurred first in nine of the men. None of them had motor disturbance as the initial feature.
With regard to APOE status, almost two-thirds of the men were homozygous e3 versus fewer than 10% who were homozygous e4. Nonetheless, the proportion of men who were homozygous e4 was significantly higher (P<0.05) than that of an age-matched normative sample, the authors reported.
"Consistent with earlier reports of boxers, our findings suggest that there may be two different clinical presentations of CTE, with one initially exhibiting behavioral or mood changes, and the other initially exhibiting cognitive impairment. The behavior/mood group demonstrated symptoms at a significantly younger age than the cognition group.
"Although almost all subjects in the behavior/mood group demonstrated cognitive impairments at some point, significantly fewer subjects in the cognition group demonstrated behavioral and mood changes during the course of their illness."
Whether the small study population is representative of all patients with CTE remains unknown, the authors noted.
The study broke new ground by attempting to identify earlier features of CTE, said Chicago psychiatrist Alex Strauss, MD, a spokesperson for the American Psychiatric Association.
"As a psychiatrist who sees a lot of concussions and traumatic brain injuries, the idea that you might have mood and behavioral issues that might be a symptom or precursor of CTE could help in determining how to manage patients," Strauss told MedPage Today. "You would need to be more cautious about sending individuals back to the field of play if there were an increased risk of developing permanent brain damage."
"Another consideration from the study relates to what kind of additional testing might be able to help us predict long-term or permanent consequences from brain trauma versus someone who might not be at risk as much," he added. "That might also help us decide who can go back to the field and who might be risking permanent brain injury."