Thursday, June 28, 2018

Age of first exposure to tackle football and chronic traumatic encephalopathy

Alosco ML, Mez J, Tripodis Y, Kiernan PT, Abdolmohammadi B, Murphy L, Kowall NW, Stein TD, Huber BR, Goldstein LE, Cantu RC, Katz DI, Chaisson CE, Martin B, Solomon TM, McClean MD, Daneshvar DH, Nowinski CJ, Stern RA, McKee AC. Age of first exposure to tackle football and chronic traumatic encephalopathy. Ann Neurol. 2018 May;83(5):886-901.

To examine the effect of age of first exposure to tackle football on chronic traumatic encephalopathy (CTE) pathological severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE.

The sample included 246 tackle football players who donated their brains for neuropathological examination. Two hundred eleven were diagnosed with CTE (126 of 211 were without comorbid neurodegenerative diseases), and 35 were without CTE. Informant interviews ascertained age of first exposure and age of cognitive and behavioral/mood symptom onset.

Analyses accounted for decade and duration of play. Age of exposure was not associated with CTE pathological severity, or Alzheimer's disease or Lewy body pathology. In the 211 participants with CTE, every 1 year younger participants began to play tackle football predicted earlier reported cognitive symptom onset by 2.44 years (p < 0.0001) and behavioral/mood symptoms by 2.50 years (p < 0.0001). Age of exposure before 12 predicted earlier cognitive (p < 0.0001) and behavioral/mood (p < 0.0001) symptom onset by 13.39 and 13.28 years, respectively. In participants with dementia, younger age of exposure corresponded to earlier functional impairment onset. Similar effects were observed in the 126 CTE-only participants. Effect sizes were comparable in participants without CTE.

In this sample of deceased tackle football players, younger age of exposure to tackle football was not associated with CTE pathological severity, but predicted earlier neurobehavioral symptom onset. Youth exposure to tackle football may reduce resiliency to late-life neuropathology. These findings may not generalize to the broader tackle football population, and informant-report may have affected the accuracy of the estimated effects.

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... 

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.”

No comments:

Post a Comment