ImportanceParkinsonism is associated with traumatic brain injury and chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head impact (RHI) exposure, but the neuropathologic substrates that underlie parkinsonism in individuals with CTE are yet to be defined.ObjectiveTo evaluate the frequency of parkinsonism in individuals with CTE and the association of RHI and neuropathologic substrates with parkinsonism in these individuals.Design, Setting, and ParticipantsThis cross-sectional study included brain donors with neuropathologically diagnosed CTE without other significant neurodegenerative disease and with information on parkinsonism from the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank between July 2015 and May 2022.ExposureYears of contact sports participation as a proxy for RHI.Main Outcomes and MeasuresThe main outcomes were frequency of parkinsonism in individuals with CTE and associations between (1) RHI with substantia nigra (SN) Lewy bodies (LBs) and neurofibrillary tangles (NFTs); (2) LBs, NFTs, and arteriolosclerosis with SN neuronal loss; and (3) SN neuronal loss, LBs, NFTs, and arteriolosclerosis with parkinsonism, tested by age-adjusted logistic regressions.ResultsOf 481 male brain donors with neuropathologically diagnosed CTE, parkinsonism occurred frequently in individuals with CTE (119 [24.7%]; 362 [75.3%] did not have parkinsonism). Participants with parkinsonism had a higher mean (SD) age at death (71.5 [13.0] years) than participants without parkinsonism (54.1 [19.3] years) (P < .001) and higher rates of dementia (104 [87.4%] vs 105 [29.0%]), visual hallucinations (45 [37.8%] vs 51 [14.1%]), and probable rapid eye movement sleep behavior disorder (52 [43.7%] vs 58 [16.0%]) (P < .001 for all). Participants with parkinsonism had a more severe CTE stage (eg, stage IV: 35 [29.4%] vs 39 [10.8%]) and nigral pathology than those without parkinsonism (NFTs: 50 of 117 [42.7%] vs 103 of 344 [29.9%]; P = .01; neuronal loss: 61 of 117 [52.1%] vs 59 of 344 [17.1%]; P < .001; and LBs: 28 of 116 [24.1%] vs 20 of 342 [5.8%]; P < .001). Years of contact sports participation were associated with SN NFTs (adjusted odds ratio [AOR], 1.04; 95% CI, 1.00-1.07; P = .03) and neuronal loss (AOR, 1.05; 95% CI, 1.01-1.08; P = .02). Nigral neuronal loss (AOR, 2.61; 95% CI, 1.52-4.47; P < .001) and LBs (AOR, 2.29; 95% CI, 1.15-4.57; P = .02) were associated with parkinsonism. However, SN neuronal loss was associated with SN LBs (AOR, 4.48; 95% CI, 2.25-8.92; P < .001), SN NFTs (AOR, 2.51; 95% CI, 1.52-4.15; P < .001), and arteriolosclerosis (AOR, 2.27; 95% CI, 1.33-3.85; P = .002). In American football players, regression analysis demonstrated that SN NFTs and neuronal loss mediated the association between years of play and parkinsonism in the context of CTE (β, 0.012; 95% CI, 0.001-0.038).Conclusions and RelevanceIn this cross-sectional study of contact sports athletes with CTE, years of contact sports participation were associated with SN tau pathology and neuronal loss, and these pathologies were associated with parkinsonism. Repetitive head impacts may incite neuropathologic processes that lead to symptoms of parkinsonism in individuals with CTE.

中文翻译：

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慢性创伤性脑病中的黑质病理学、接触性运动和帕金森病


重要性帕金森症与创伤性脑损伤和慢性创伤性脑病 (CTE) 相关，慢性创伤性脑病 (CTE) 是一种与重复性头部撞击 (RHI) 暴露相关的神经退行性疾病，但 CTE 个体帕金森症背后的神经病理学基础尚未明确。患有 CTE 的个体中的帕金森氏症以及 RHI 和神经病理学底物与这些个体中的帕金森氏症的关联。设计、设置和参与者这项横断面研究包括患有神经病理学诊断的 CTE 且没有其他显着神经退行性疾病的脑供体，并包含来自理解神经学的帕金森氏症信息2015 年 7 月至 2022 年 5 月之间的损伤和创伤性脑病脑库。暴露参与接触运动的年数作为 RHI 的代理。主要结果和措施主要结果是患有 CTE 的个体帕金森病的频率以及 (1) RHI 与黑质 (SN) 之间的关联) 路易体 (LB) 和神经原纤维缠结 (NFT)； (2) LB、NFT 和动脉硬化伴 SN 神经元丢失； (3) SN 神经元丢失、LB、NFT 和动脉硬化伴帕金森病，通过年龄调整逻辑回归进行测试。结果在 481 名经神经病理学诊断为 CTE 的男性脑捐献者中，帕金森病频繁发生在患有 CTE 的个体中 (119 [24.7%]；362 [75.3%]没有帕金森症）。帕金森症患者的平均 (SD) 年龄（71.5 [13.0] 岁）高于非帕金森症患者的平均死亡年龄（54.1 [19.3] 岁）（P < .001），痴呆症发病率也较高（104 [87.4%] vs. 105 [29.0%]），幻视（45 [37.8%] vs 51 [14.1%]），以及可能的快速动眼睡眠行为障碍（52 [43.7%] vs 58 [16.0%]）（所有 P < .001）。与无帕金森病的参与者相比，患有帕金森病的参与者具有更严重的 CTE 阶段（例如，IV 期：35 [29.4%] vs 39 [10.8%]）和黑质病理（NFT：117 人中的 50 人 [42.7%] vs 344 人中的 103 人 [29.9] %]; 神经元损失：117 中的 61 个 [52.1%] 与 344 中的 59 个 [17.1%]；并且 LB：116 中的 28 个 [24.1%] 与 342 中的 20 个 [5.8%] ]；P＜0.001)。参与接触运动的年数与 SN NFT（调整后优势比 [AOR]，1.04；95% CI，1.00-1.07；P = 0.03）和神经元损失（AOR，1.05；95% CI，1.01-1.08；P）相关。 = .02)。黑质神经元丢失（AOR，2.61；95% CI，1.52-4.47；P < .001）和 LB（AOR，2.29；95% CI，1.15-4.57；P = 0.02）与帕金森症相关。然而，SN 神经元丢失与 SN LB（AOR，4.48；95% CI，2.25-8.92；P < .001）、SN NFT（AOR，2.51；95% CI，1.52-4.15；P < .001）相关。 ）和动脉硬化（AOR，2.27；95% CI，1.33-3.85；P = .002）。在美国橄榄球运动员中，回归分析表明，在 CTE 背景下，SN NFT 和神经元损失介导了比赛年限与帕金森病之间的关联（β，0.012；95% CI，0.001-0.038）。结论和相关性在这项横断面研究中在患有 CTE 的接触性运动运动员中，参与接触性运动的年数与 SN tau 病理学和神经元损失有关，而这些病理学与帕金森症有关。重复的头部撞击可能会引发神经病理过程，导致 CTE 患者出现帕金森病症状。