Nearly one-quarter of deceased athletes with chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head impacts, experienced Parkinson’s disease-like symptoms during their lives, according to a study researchers said is the largest to date exploring the links among contact sports, CTE, and parkinsonism.
The researchers found that the association between CTE and parkinsonism was mostly mediated by neuronal loss and accumulation of tau proteins in a region of the brain involved in motor control rather than the presence of Lewy bodies, a hallmark feature of Parkinson’s disease.
“This study underscores the importance of understanding the long-term effects of repetitive head impacts and the need for preventive measures in contact sports to mitigate the risk of neurodegenerative diseases like CTE and parkinsonism,” they wrote in the study, “Substantia Nigra Pathology, Contact Sports Play, and Parkinsonism in Chronic Traumatic Encephalopathy,” published in JAMA Neurology.
Parkinson’s disease is caused by the progressive death of dopaminergic neurons, nerve cells that produce a major brain chemical messenger called dopamine. These neurons are primarily found in the substantia nigra, a brain region involved in motor control. A key characteristic of the disease is the formation of abnormal clumps of alpha-synuclein in brain cells, known as Lewy bodies.
Mechanism of CTE-parkinsonism link studied
Parkinsonism is a condition marked by symptoms similar to Parkinson’s disease, including tremor, slowness of movements, and muscle stiffness. The condition has been associated with traumatic brain injury — when a violent blow or shake to the head causes brain damage — and CTE.
CTE is normally marked by the present of deposits of the tau protein within fiber-like structures called neurofibrillary tangles (NFTs). Research has also shown that years of American football participation is associated with higher odds of developing Lewy body disease, but “the specific [mechanisms] underlying these [parkinsonism] in CTE were unknown,” the researchers, from Boston University Chobanian and Avedisian School of Medicine and VA Boston Healthcare, wrote.
They set out to determine the frequency of parkinsonism in people with CTE, as well as the exact molecular mechanisms linking the two conditions.
The team analyzed brain samples from 481 deceased men who had played contact sports and been diagnosed with CTE. The athletes had donated their brains to the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank at Boston University.
Based on interviews, online surveys, and reviews of medical data, the team determined that 24.7% of patients in their sample had experienced parkinsonism during their lives. There were no differences in the number of years of contact sport participation between people with and without parkinsonism, but the primary sport for those who had parkinsonism was more frequently American football (90.8% vs. 84.3%).
Individuals with parkinsonism had significantly more severe CTE and were more likely to have Lewy body disease (24.1% vs. 5.8%). The presence of neurofibrillary tangles and severe neuronal loss was also more frequent in individuals with parkinsonism.
But notably, most participants with parkinsonism lacked Lewy bodies in the substantia nigra, suggesting that most cases of parkinsonism in people with CTE are instead driven by the neurofibrillary tangles and severe neuronal loss.
“We were surprised to find that most individuals with CTE and parkinsonism did not have Lewy body pathology,” Thor Stein, MD, PhD, one of the corresponding authors of the study, said in a press release. “Rather, subjects with parkinsonism were more likely to have more severe CTE-related brain cell death” in the substantia nigra, Stein said.
The team also tested whether practicing contact sports for longer periods — which in theory would result in greater exposure to repeat head injuries — was linked to more severe damage leading up to parkinsonism.
They found that each year of contact sport participation was associated with a 4% higher likelihood of having neurofibrillary tangles and a 5% higher chance of neuronal loss in the substantia nigra. However, there was no link between added years of contact sports and the presence of Lewy bodies in the substantia nigra.
“Overall, this suggests that an additional approximately 8 to 10 years of contact sports play is associated with 50% increased risk of moderate-severe nigral [disease],” the researchers wrote.