黑质病理学、接触性运动、慢性创伤性脑病中的帕金森病。

Substantia Nigra Pathology, Contact Sports Play, and Parkinsonism in Chronic Traumatic Encephalopathy.

机构信息

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts.

Department of Neurosciences, University of California, San Diego School of Medicine, La Jolla.

出版信息

JAMA Neurol. 2024 Sep 1;81(9):916-924. doi: 10.1001/jamaneurol.2024.2166.

DOI:10.1001/jamaneurol.2024.2166

PMID:39008284

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11250391/

Abstract

IMPORTANCE

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.

OBJECTIVE

To 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 PARTICIPANTS: 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.

EXPOSURE

Years of contact sports participation as a proxy for RHI.

MAIN OUTCOMES AND MEASURES

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.

RESULTS

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).

CONCLUSIONS AND RELEVANCE

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.

摘要

重要性

帕金森病与创伤性脑损伤和慢性创伤性脑病（CTE）有关，这是一种与重复头部撞击（RHI）暴露相关的神经退行性疾病，但 CTE 患者中帕金森病的神经病理学基础尚未确定。

目的

评估 CTE 患者中帕金森病的频率，以及 RHI 和神经病理学基础与这些患者帕金森病的关联。

设计、地点和参与者：这项横断面研究纳入了神经病理学诊断为 CTE 且无其他显著神经退行性疾病的脑捐献者，以及 2015 年 7 月至 2022 年 5 月期间来自理解神经损伤和创伤性脑病脑库的帕金森病信息。

暴露

接触性运动年限作为 RHI 的替代指标。

主要结局和测量

主要结局为 CTE 患者中帕金森病的频率，以及（1）RHI 与黑质（SN）路易体（LB）和神经纤维缠结（NFT）的关联；（2）LB、NFT 和小动脉粥样硬化与 SN 神经元丢失的关联；（3）SN 神经元丢失、LB、NFT 和小动脉粥样硬化与帕金森病的关联，通过年龄调整的逻辑回归进行测试。

结果

在 481 名神经病理学诊断为 CTE 的男性脑捐献者中，帕金森病在 CTE 患者中很常见（119 例[24.7%]；362 例[75.3%]没有帕金森病）。患有帕金森病的参与者的平均（SD）死亡年龄（71.5 [13.0] 岁）高于无帕金森病的参与者（54.1 [19.3] 岁）（P<0.001），并且痴呆症（104 例[87.4%] vs 105 例[29.0%]）、视幻觉（45 例[37.8%] vs 51 例[14.1%]）和可能的快速眼动睡眠行为障碍（52 例[43.7%] vs 58 例[16.0%]）的发生率更高（所有 P<0.001）。患有帕金森病的参与者的 CTE 分期更严重（例如，IV 期：35 例[29.4%] vs 39 例[10.8%]），黑质病理学比无帕金森病的参与者更严重（NFT：117 例中的 50 例[42.7%] vs 344 例中的 103 例[29.9%]；P=0.01；神经元丢失：117 例中的 61 例[52.1%] vs 344 例中的 59 例[17.1%]；P<0.001；LB：116 例中的 28 例[24.1%] vs 342 例中的 20 例[5.8%]；P<0.001）。接触性运动年限与 SN NFT（调整后的优势比[OR]，1.04；95%置信区间[CI]，1.00-1.07；P=0.03）和神经元丢失（OR，1.05；95% CI，1.01-1.08；P=0.02）相关。黑质神经元丢失（OR，2.61；95% CI，1.52-4.47；P<0.001）和 LB（OR，2.29；95% CI，1.15-4.57；P=0.02）与帕金森病相关。然而，SN 神经元丢失与 SN LB（OR，4.48；95% CI，2.25-8.92；P<0.001）、SN NFT（OR，2.51；95% CI，1.52-4.15；P<0.001）和小动脉粥样硬化（OR，2.27；95% CI，1.33-3.85；P=0.002）相关。在美式足球运动员中，回归分析表明，SN NFT 和神经元丢失介导了运动年限与 CTE 背景下帕金森病之间的关联（β，0.012；95% CI，0.001-0.038）。