■帕金森病与创伤性脑损伤和慢性创伤性脑病(CTE)有关,与重复性头部撞击(RHI)暴露相关的神经退行性疾病,但CTE患者帕金森病的神经病理学基础尚待确定.
■评估患有CTE的个体中帕金森病的频率以及这些个体中RHI和神经病理学底物与帕金森病的关联。
■这项横断面研究包括2015年7月至2022年5月期间,经神经病理学诊断为CTE而无其他重大神经退行性疾病的脑供体,以及来自“理解神经损伤和创伤性脑病”脑库的帕金森病信息。
■多年的接触体育参与作为RHI的代理。
■主要结果是CTE患者的帕金森病频率以及(1)RHI与黑质(SN)路易体(LBs)和神经原纤维缠结(NFT)之间的关联;(2)LBs,NFTs,和动脉粥样硬化伴SN神经元丢失;和(3)SN神经元丢失,LBs,NFTs,动脉硬化伴帕金森综合征,通过年龄调整逻辑回归检验。
■在481名患有神经病理学诊断CTE的男性大脑捐献者中,在CTE患者中经常发生帕金森病(119例[24.7%];362例[75.3%]没有帕金森病).患有帕金森病的参与者死亡时的平均(SD)年龄(71.5[13.0]岁)高于没有帕金森病的参与者(54.1[19.3]岁)(P<.001),痴呆的发生率更高(104[87.4%]vs105[29.0%]),视觉幻觉(45[37.8%]vs51[14.1%]),和可能的快速眼动睡眠行为障碍(52[43.7%]vs58[16.0%])(全部P<.001)。患有帕金森病的参与者有更严重的CTE阶段(例如,IV期:35[29.4%]vs39[10.8%])和非病理学比没有帕金森病的患者(NFT:117中的50[42.7%]vs344中的103[29.9%];P=.01;神经元丢失:117中的61[52.1%]vs344中的59[17.1%];P<.001;LBs:116中的28[24.1%]vs342中的20多年的接触运动参与与SNNFT相关(调整后的优势比[AOR],1.04;95%CI,1.00-1.07;P=0.03)和神经元丢失(AOR,1.05;95%CI,1.01-1.08;P=.02)。黑质神经元丢失(AOR,2.61;95%CI,1.52-4.47;P<.001)和LBs(AOR,2.29;95%CI,1.15-4.57;P=.02)与帕金森病相关。然而,SN神经元丢失与SNLBs(AOR,4.48;95%CI,2.25-8.92;P<.001),SNNFTs(AOR,2.51;95%CI,1.52-4.15;P<.001),和动脉硬化(AOR,2.27;95%CI,1.33-3.85;P=.002)。在美国足球运动员中,回归分析表明,在CTE的背景下,SNNFT和神经元丢失介导了游戏年限和帕金森病之间的关联(β,0.012;95%CI,0.001-0.038)。
■在这项对接触运动运动员与CTE的横断面研究中,多年的接触运动参与与SNtau病理和神经元丢失有关,这些病理与帕金森病有关。重复的头部撞击可能会引起神经病理学过程,从而导致CTE患者出现帕金森病症状。
UNASSIGNED: Parkinsonism 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.
UNASSIGNED: To evaluate the frequency of parkinsonism in individuals with CTE and the association of RHI and neuropathologic substrates with parkinsonism in these individuals.
UNASSIGNED: This 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.
UNASSIGNED: Years of contact sports participation as a proxy for RHI.
UNASSIGNED: The 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.
UNASSIGNED: Of 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).
UNASSIGNED: In 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.