Pathological associations with parkinsonism in chronic traumatic encephalopathy

Abstract

AbstractBackgroundParkinsonism has been shown to be more frequent in those with a history of traumatic brain injury, repetitive head impacts (RHI), and chronic traumatic encephalopathy (CTE), a disease characterized by tau pathology. However, the underlying pathological associations with parkinsonism in this context are not well known.MethodsAutopsy participants with a history of RHI exposure through contact sports participation and neuropathologically diagnosed with CTE (n = 481) were examined for pathology in the substantia nigra. Based on review of next‐of‐kin interviews and medical records, expert clinicians judged whether symptoms of parkinsonism, including bradykinesia, resting tremor, rigidity, micrographia, and shuffling gait, were present. The total number of consecutive years of contact sports play was used as a proxy for RHI exposure. Neuropathological diagnoses were made using established criteria. Pathology in the substantia nigra was quantified for alpha‐synuclein‐positive Lewy bodies, neurofibrillary tangles (NFTs), and neuronal loss.ResultsOf a total of 481 male CTE participants, 119 (24.7%) had symptoms of parkinsonism during life. Comparison of clinical characteristics of CTE participants with (n = 119) and without (n = 362) parkinsonism showed those with parkinsonism had an older age of death, and a larger proportion had symptoms of dementia, probable REM sleep behavior disorder, and visual hallucinations than participants without parkinsonism (p’s <0.00001). Of those with CTE and parkinsonism, the majority (70%) did not have Lewy bodies within the substantia nigra, suggesting other pathologies may also contribute to motor symptoms. In fact, those with parkinsonism were more likely to have nigral NFTs and neuronal loss (Figure), adjusting for age as well as when restricting to those age >65 (p’s<0.001). Years of contact sports play was associated with NFTs (p = 0.03) and neuronal loss (p = 0.016), but not Lewy bodies in the substantia nigra. Both nigral NFTs (p = 0.001) and Lewy bodies (p<0.001) were associated with nigral neuronal loss. Parkinsonism was associated with neuronal loss (p<0.001) and Lewy bodies (p = 0.027) in the substantia nigra.ConclusionOverall, these findings suggest that RHI contributes to tau pathology and neuronal loss in the substantia nigra. Those susceptible to Lewy body pathology may be further at risk for parkinsonism in CTE.