ARTICLE IN BRIEF
Age of first exposure to tackle football was associated with the earlier onset of mood and cognitive symptoms in people who had neuropathologically-confirmed chronic traumatic encephalopathy.
In a post-mortem analysis of amateur and professional tackle football players with neuropathologically-confirmed chronic traumatic encephalopathy (CTE), researchers identified an association between the age of first exposure to the sport and the development of neurobehavioral symptoms later in life. Athletes with CTE who had been exposed to tackle football before age 12 had earlier onset of cognitive and mood problems by more than an average of 13 years, according to the study published online April 30 in Annals of Neurology.
Among the 211 participants with confirmed CTE, 183 developed both cognitive and behavioral/mood symptoms before death. “Every one year younger that participants began to play football resulted in earlier reported onset of cognitive and behavioral mood symptoms by approximately 2.5 years,” the researchers wrote. “These findings were independent of level (i.e., high school, college, professional) and duration of play.”
The study authors noted, however, that they found no association between the age of first exposure to the tackle football and the severity of CTE.
“We hypothesized that starting to play at such a young age could interfere with neurodevelopment,” said the first study author Michael L. Alosco, PhD, a postdoctoral fellow at the Boston University Alzheimer's Disease and Chronic Traumatic Encephalopathy Center. “Similar effects on neurobehavioral symptoms were observed in participants without CTE, suggesting that the relationship between younger age of exposure to tackle football and long term neurobehavioral disturbances may not be specific to CTE,” Dr. Alosco said.
“It could be CTE, Alzheimer's disease, or other diseases that affect the brain,” he continued. “This relationship is not just seen in CTE, but in other types of brain diseases.”
Dr. Alosco and his colleagues acknowledged that both ascertainment and recall bias could have factored into the analysis in the study population. “There's also a possible selection bias. People who had symptoms were more likely to struggle in life and donate their brain,” he told Neurology Today.
“A message that we're trying to communicate is that CTE in these findings is not about concussion, but repeated head impacts; the tiny hits to the head that add up,” Dr. Alosco said. “It's ultimately up to the parent to weigh the risks and benefits of what we know and make a decision,” Dr. Alosco added.
In the study, researchers examined the brains of 246 deceased amateur and professional football players who donated their brains to the Veterans Affairs-Boston University-Concussion Legacy Foundation Brain Bank. Approximately 211 players had CTE.
To assess the medical and clinical history related to cognitive and neuropsychiatric function, researchers used online questionnaires and retrospective telephone clinical interviews with informants of participants. Informants revealed the absence or presence and age of onset of cognitive and behavior/mood symptoms in the deceased participants. They also analyzed data on sports played, level, position, age of first exposure to football, as well as duration and history of traumatic brain injury (TBI).
“Neuropathological criteria for CTE require at least one perivascular lesion of p-tau aggregates in neurons as neurofibrillary tangles (NFTs), astrocytes, and cell processes around a small vessel, typically found at the sulcal depths (‘CTE lesion’),” the researchers wrote.
The researchers defined CTE pathological severity using a provisional four stage classification scheme (one for the least severe and four, the most severe) dependent on the extent and severity of tau pathology.
The researchers concluded that the clinical manifestation of CTE involves early-life behavioral/mood symptoms and/or later-life cognitive impairment. In most cases of CTE, cognitive dysfunction was present, while those with cognitive impairment as an initial symptom are more likely to develop dementia.
Of the 211 players with CTE, 89 had other neurogenerative diseases, including Alzheimer's disease, Lewy body disease, frontotemporal lobar degeneration (FTLD), motor neuron disease, and/or prion disease. Twenty six of the 35 participants without CTE showed signs of other diseases, as well, including Alzheimer's disease, FTLD, Lewy body disease, moderate to severe vascular disease (based on arteriolosclerosis and/or atherosclerosis), unspecified tauopathy, and non-specific changes (for example, heme-laden macrophages, axonal injury).
Despite the findings, the mechanisms involved in the link between age of first exposure to tackle football and earlier symptom onset remain undefined.
Rodolfo Savica, MD, PhD, associate professor of neurology and epidemiology, senior associate consultant in the department of neurology and health science research at Mayo Clinic in Rochester, MN, commented that that ascertainment and recall bias might have factored into the findings — first, with the cohort used in the study and then with the method they used to explore CTE-related symptoms.
“These participants were willing to explore the possibility of having degeneration from playing football,” Dr. Savica said. “To assess the cognitive problems, they [the researchers] used informants, so it's not a prospective study about possible [CTE-related] symptoms.”
Bert Vargas, MD, FAHS, FAAN, an associate professor of neurology at UT Southwestern in Dallas, said: “We must be cautious when interpreting retrospective data from small subsets of the population — even the authors suggest exercising caution when making attempts to extrapolate this to a larger population of current and former football players.”
“Most of the patients in this study (and in most other post-mortem or long-term studies) played in an era where repeated concussions were frequently not identified or recognized as as having potential long-term consequences, both of which may have adversely affected their clinical and pathological outcomes,” Dr. Vargas said.
Christopher Giza, MD, professor of pediatric neurology at the University of California, Los Angeles, agreed. He noted that there are many unaccounted variables, such as duration and intensity of exposure, educational level, genetics, exposures to other drugs, such as performance-enhancing drugs and opiates, that can influence neuropathology and behavior symptoms.
“Cognitive, behavioral, and mood symptoms have many potential causes. Prospectively in clinic patients, we and others see many treatable comorbidities that may cause similar symptoms,” he told Neurology Today.
Dr. Giza also advised doctors to exercise caution when evaluating CTE-related symptoms. “For medical providers who are caring for these patients, it is critically important to determine what underlying diagnoses may be causing symptoms (chronic headaches, learning problems, anxiety, depression, endocrine problems, sleep disturbances, etc.) and then to treat them.”
Dr. Giza also thought that the authors' hypothesis that younger age exposure to tackle football may potentially reduce resiliency to late life neuropathology is an important one, but difficult to answer with this type of study. An alternative hypothesis is that repeated impacts or subconcussive hits may interfere with brain development during critical periods, he said.
“However, studies like the current study are not actually capable of answering that hypothesis,” he continued. “There are no measures for impacts, and the authors acknowledged there may be an ascertainment bias and a recall bias.”
Among other challenges, Dr. Giza said, it is difficult to rigorously control for differences in age at first exposure versus duration of exposure, and the criteria for clinical symptomatology are broad and not specific for CTE or any other dementia for that matter.
“Unfortunately, there is no simple way to generalize this to a population of living former football or contact sports players who are now aging and reporting symptoms,” Dr. Giza added.
Dr. Vargas suggested that building resilience and cognitive reserve is important and potentially helpful for every individual, “as exposure to concussion and repetitive head trauma is certainly not limited to athletes in contact sports.”