Parkinsonism Risk: Athletes With CTE Show Tau Pathology, Neuronal Loss in Substantia Nigra

Among former athletes with chronic traumatic encephalopathy (CTE), years of playing contact sports were associated with evidence of substantia nigra (SN) tau pathology and neuronal loss, according to a post-mortem analysis published in JAMA Neurology.

Although head injuries have been previously linked with the development of parkinsonism and Lewy body pathology, the exact pathophysiologic mechanism remains unclear.

Researchers conducted a cross-sectional study to evaluate the incidence of parkinsonism in patients with CTE and assess the links between repetitive head impacts (RHI), SN pathology, and parkinsonism.

The primary outcome of interest was the frequency of parkinsonism and the presence of SN pathology in deceased men who had a history of RHI associated with CTE.

The researchers sourced autopsy data from the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank from July 2015 to May 2022. Eligible participants included deceased men diagnosed with confirmed CTE and those who did not have significant comorbid conditions (N=495).

The current analysis included 481 men autopsy participants with CTE and comprehensive data. Among them, 119 exhibited parkinsonism, with a mean age at death of 71.5 years, significantly older than individuals without parkinsonism, who had a mean age of 54.1 years.

The parkinsonism group showed a higher prevalence of symptoms such as dementia (87.4% vs 29%), probable rapid eye movement sleep behavior disorder (43.7% vs 16%), and visual hallucinations (37.8% vs 14.1%; P <.001 for all).

American football was the predominant sport among individuals with parkinsonism (90.8% vs 84.3%), while the total years of participation in contact sports were comparable between both groups (P =.69).

Neuropathological findings revealed that individuals with parkinsonism exhibited significantly higher levels of CTE (P <.001) and were more likely to have Lewy body disease, with rates of 29.4% vs 9.4% in others (P <.001). The incidence of neocortical Lewy body disease was also elevated, at 51.4% vs 11.8% (P <.001).

Additionally, moderate to severe arteriolosclerosis was more common among individuals with parkinsonism, occurring in 68.1% vs 37.6% (P <.001). While nigral Lewy bodies were found more frequently in the parkinsonism group (24.1% vs 5.8%; P <.001), the majority of individuals with parkinsonism (76%) did not have these bodies present.

Moderate to severe neuronal loss (adjusted odds ratio [aOR], 2.61; 95% CI, 1.52-4.47; P <.001) and the presence of nigral Lewy bodies (aOR, 2.29; 95% CI, 1.15-4.57; P =.02) are associated with an increased likelihood of developing parkinsonism.

Study limitations included a small, selective sample of men contact sports players with CTE, potential recall bias, lack of prospective assessments, and an inability to discern drug-induced parkinsonism.

“The findings suggest that extensive RHI is associated with parkinsonism through increased tau pathology and neuronal loss, even in the absence of Lewy pathology,” the researchers concluded.

This research was supported by the Department of Veterans Affairs, Veterans Health Administration; the Veterans Affairs Biorepository; the Alzheimer’s Association; the National Institute of General Medical Sciences; the National Institute on Aging; the National Institute of Neurological Disorders and Stroke; the Boston University Alzheimer’s Disease Research Center; the Department of Defense Peer Reviewed Alzheimer’s Research Program; the NIH; and the Concussion Legacy Foundation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.