medwireNews: Parkinsonism in people with chronic traumatic encephalopathy (CTE) due to sport-related repetitive head injury is linked to substantia nigra (SN) tau pathology and neuronal loss, a study has found.
Patients with CTE who had parkinsonism were significantly more likely than those without to have Lewy bodies (LBs), moderate-to-severe neurofibrillary tangles (NFTs), and moderate-to-severe neuronal loss.
The results also showed that among the 86.9% of the participants who played American football specifically, every 10.3 and 8.3 additional years of playing significantly increased the risk for moderate-severe NFTs and neuronal loss in the SN by 50%, with corresponding adjusted odds ratios of 1.04 and 1.05.
“We observed that years of contact sports participation and SN neuronal loss were associated with nigral NFTs, which were nearly twice as common as LBs in individuals with parkinsonism, and that SN neuronal loss, in turn, was associated with parkinsonism,” write Ann McKee (Boston University, Massachusetts, USA) and colleagues in JAMA Neurology.
The SN accumulates a high burden of pathological tau as CTE progresses, they note, adding that the findings “indicate nigral susceptibility to damage and degeneration following head injury.”
The cross-sectional study used data for 481 men with a history of exposure to repetitive head injury from playing contact sports, primarily American football, and a neuropathological diagnosis of CTE who donated their brains for research. Eligible participants did not have comorbidities such as Alzheimer’s disease, frontotemporal lobar degeneration, and motor neuron disease.
Parkinsonism developed in 24.7% of individuals and these participants lived significantly longer than the remaining participants without the condition, with a mean age at death of 71.5 versus 54.1 years. A respective 79.8% and 76.8% of the participants with and without parkinsonism were White.
McKee and colleagues found that participants with parkinsonism had significantly higher rates than those without of dementia (87.4% vs 29.0%), visual hallucinations (37.8% vs 14.1%), and probable rapid eye movement sleep behavior disorder (43.7% vs 16.0%).
They also observed more severe CTE in the parkinsonism group, which ranges from stage I (confusion, disorientation) to stage IV (progressive dementia, movement disorders and hypomimia). A total of 48.7% and 29.4% of those with parkinsonism were at stages III and IV, respectively, compared with a corresponding 36.2% and 10.8% among those without parkinsonism. The former group were also significantly more likely than the latter group to have moderate-severe arteriolosclerosis, at 68.1% versus 37.6%.
Regarding SN pathology, significantly more participants with than without parkinsonism had a higher semiquantitative burden of neurofibrillary tangles (42.7 vs 29.9%) and neuronal loss (52.1 vs 17.1%).
And while patients with parkinsonism were more likely to have LBs than those without (24.1 vs 5.8%), they were found in only a minority of the patients, suggesting “other, nonsynuclein pathology may be associated with parkinsonism in some participants,” the researchers note.
Nevertheless, both SN LBs and neuronal loss were significantly linked to increased risk for parkinsonism, with adjusted odds ratios of 2.29 and 2.61, respectively. And LBs, NFTs, and arteriolosclerosis were all significantly associated with SN neuronal loss, with respective adjusted odds ratios of 4.48, 2.51, and 2.27.
One of the study limitations cited by McKee et al was that the clinical data came from a retrospective review and not prospectively, making them potentially subject to recall bias. Another was that there were few brain donors without CTE who had parkinsonism, making the study population difficult to extrapolate to other groups.
In an editorial related to the study, Breton Asken (University of Florida, Gainesville, USA) and colleagues note that the results “shed light on the potential neuropathological underpinnings of the increased risk for parkinsonism in individuals with prior [repetitive head injury].”
They add: “To better understand potential clinical signatures of [repetitive head injury]-associated parkinsonism, it is critical for future research efforts in Parkinson disease and parkinsonism to ask about lifetime exposure to [traumatic brain injury] as well as possible sources of [repetitive head injury] like contact sport play during routine movement disorders evaluations.”
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JAMA Neurol 2024; doi:10.1001/jamaneurol.2024.2166
JAMA Neurol 2024; doi:10.1001/jamaneurol.2024.2162
