Sheina Emrani, Anne Koutures, Yorghos Tripodis, Madeline Uretsky, Bobak Abdolmohammadi, Christopher Nowinski, Daniel H. Daneshvar, Brigid Dwyer, Douglas I. Katz, Lee E. Goldstein, Robert C. Cantu, Brett M. Martin, Joseph N. Palmisano, Kristen Dams-O’Connor, John F. Crary, Robert A. Stern, Jesse Mez, Victor E. Alvarez, Bertrand R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
{"title":"确定受到重复性头部撞击的大脑捐献者体内白质和血管病变的特征","authors":"Sheina Emrani, Anne Koutures, Yorghos Tripodis, Madeline Uretsky, Bobak Abdolmohammadi, Christopher Nowinski, Daniel H. Daneshvar, Brigid Dwyer, Douglas I. Katz, Lee E. Goldstein, Robert C. Cantu, Brett M. Martin, Joseph N. Palmisano, Kristen Dams-O’Connor, John F. Crary, Robert A. Stern, Jesse Mez, Victor E. Alvarez, Bertrand R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco","doi":"10.1007/s00401-025-02860-z","DOIUrl":null,"url":null,"abstract":"<div><p>Chronic traumatic encephalopathy (CTE) is a progressive brain disease linked to repetitive head impacts (RHI), often incurred from contact sports, and can lead to dementia. Here, we investigated the association between RHI and white matter/vascular neuropathologies and their relative contribution to dementia status in deceased men 50 + years old with and without exposure to RHI from various types of contact and collision sports. Our sample included two RHI groups from the UNITE brain bank: (1) American Football players (RHI-AF, <i>n</i> = 79), and (2) non-AF contact and collision sport athletes (e.g., boxing, rugby; RHI-CCS, <i>n</i> = 49). Controls included similarly aged (± 5 years) male brain donors without RHI. A modified ischemic injury scale (mIIS) served as a global measure of white matter and vascular neuropathologies, encompassing nine subcomponents. Dementia was determined through diagnostic consensus conference based on interviews with families. Using linear regression models controlling for age at death, mIIS was different in RHI-AF versus non-RHI only (<i>p</i> = 0.036). Subsequent logistic regression of each mIIS subcomponent, controlling for age at death, demonstrated that worse white matter rarefaction (RHI-AF; Beta = 1.42, [95% CI 2.03–8.43]; RHI-CCS; Beta = 1.93, [95% CI 2.35–20.17]) and hippocampal sclerosis (RHI-AF; Beta = 2.01, [95% CI 2.69–20.81]; RHI-CCS; Beta = 2.19, [95% CI 2.49–32.10]) was more common in RHI groups from their controls. Further, logistic regressions found that higher global mIIS correlated with increased odds of dementia in only the RHI-AF group (<i>p</i> = 0.02), driven by white matter rarefaction (<i>β</i> = 0.94, [95% CI 1.66–4.00]) and hippocampal sclerosis (<i>β</i> = 1.08, [95% CI 1.35–6.42]). There were similar findings in RHI-CCS group for odds of dementia (<i>p</i> = 0.048), including white matter rarefaction (<i>β</i> = 0.68, [95% CI 1.22–3.21], <i>p</i> = 0.05). Overall, these results demonstrate that white matter rarefaction and hippocampal sclerosis are linked to RHI exposure across all types of contact sports. Further, these pathologies contribute to dementia independent of p-tau pathology in American football players.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"149 1","pages":""},"PeriodicalIF":9.3000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02860-z.pdf","citationCount":"0","resultStr":"{\"title\":\"Characterizing white matter and vascular pathologies in brain donors exposed to repetitive head impacts\",\"authors\":\"Sheina Emrani, Anne Koutures, Yorghos Tripodis, Madeline Uretsky, Bobak Abdolmohammadi, Christopher Nowinski, Daniel H. Daneshvar, Brigid Dwyer, Douglas I. Katz, Lee E. Goldstein, Robert C. Cantu, Brett M. Martin, Joseph N. Palmisano, Kristen Dams-O’Connor, John F. Crary, Robert A. Stern, Jesse Mez, Victor E. Alvarez, Bertrand R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco\",\"doi\":\"10.1007/s00401-025-02860-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Chronic traumatic encephalopathy (CTE) is a progressive brain disease linked to repetitive head impacts (RHI), often incurred from contact sports, and can lead to dementia. Here, we investigated the association between RHI and white matter/vascular neuropathologies and their relative contribution to dementia status in deceased men 50 + years old with and without exposure to RHI from various types of contact and collision sports. Our sample included two RHI groups from the UNITE brain bank: (1) American Football players (RHI-AF, <i>n</i> = 79), and (2) non-AF contact and collision sport athletes (e.g., boxing, rugby; RHI-CCS, <i>n</i> = 49). Controls included similarly aged (± 5 years) male brain donors without RHI. A modified ischemic injury scale (mIIS) served as a global measure of white matter and vascular neuropathologies, encompassing nine subcomponents. Dementia was determined through diagnostic consensus conference based on interviews with families. Using linear regression models controlling for age at death, mIIS was different in RHI-AF versus non-RHI only (<i>p</i> = 0.036). Subsequent logistic regression of each mIIS subcomponent, controlling for age at death, demonstrated that worse white matter rarefaction (RHI-AF; Beta = 1.42, [95% CI 2.03–8.43]; RHI-CCS; Beta = 1.93, [95% CI 2.35–20.17]) and hippocampal sclerosis (RHI-AF; Beta = 2.01, [95% CI 2.69–20.81]; RHI-CCS; Beta = 2.19, [95% CI 2.49–32.10]) was more common in RHI groups from their controls. Further, logistic regressions found that higher global mIIS correlated with increased odds of dementia in only the RHI-AF group (<i>p</i> = 0.02), driven by white matter rarefaction (<i>β</i> = 0.94, [95% CI 1.66–4.00]) and hippocampal sclerosis (<i>β</i> = 1.08, [95% CI 1.35–6.42]). There were similar findings in RHI-CCS group for odds of dementia (<i>p</i> = 0.048), including white matter rarefaction (<i>β</i> = 0.68, [95% CI 1.22–3.21], <i>p</i> = 0.05). Overall, these results demonstrate that white matter rarefaction and hippocampal sclerosis are linked to RHI exposure across all types of contact sports. Further, these pathologies contribute to dementia independent of p-tau pathology in American football players.</p></div>\",\"PeriodicalId\":7012,\"journal\":{\"name\":\"Acta Neuropathologica\",\"volume\":\"149 1\",\"pages\":\"\"},\"PeriodicalIF\":9.3000,\"publicationDate\":\"2025-03-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s00401-025-02860-z.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Neuropathologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00401-025-02860-z\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Neuropathologica","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00401-025-02860-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
慢性创伤性脑病（CTE）是一种与重复性头部撞击（RHI）有关的进行性脑部疾病，通常由接触性运动引起，并可导致痴呆。在这里，我们调查了RHI和白质/血管神经病变之间的关系，以及它们对痴呆症状态的相对贡献，研究对象是50岁以上的男性，无论他们是否因各种类型的接触和碰撞运动而暴露于RHI。我们的样本包括来自UNITE脑库的两个RHI组：(1)美式橄榄球运动员（RHI- af, n = 79）和(2)非af接触和碰撞运动运动员(如拳击、橄榄球；RHI-CCS, n = 49)。对照组包括同样年龄（±5岁）的无RHI的男性脑供体。改良的缺血性损伤量表（mIIS）作为白质和血管神经病变的全面测量，包括九个亚组分。痴呆症是通过基于家庭访谈的诊断共识会议确定的。使用控制死亡年龄的线性回归模型，仅RHI-AF组与非rhi组的mIIS不同（p = 0.036）。随后，在控制死亡年龄的情况下，对每个mIIS子成分进行logistic回归分析，结果显示白质稀疏程度更差(RHI-AF；贝塔系数= 1.42,[95% CI 2.03-8.43]；RHI-CCS;β = 1.93, [95% CI 2.35-20.17])和海马硬化(RHI-AF；贝塔系数= 2.01,[95% CI 2.69-20.81]；RHI-CCS;β = 2.19, [95% CI 2.49-32.10])在RHI组中比对照组更常见。此外，logistic回归发现，只有在RHI-AF组中，较高的总体mIIS与痴呆发生率增加相关（p = 0.02），这是由白质稀疏（β = 0.94, [95% CI 1.66-4.00]）和海马硬化（β = 1.08, [95% CI 1.35-6.42]）驱动的。RHI-CCS组痴呆的发生率相似（p = 0.048），包括白质稀疏（β = 0.68, [95% CI 1.22-3.21], p = 0.05）。总的来说，这些结果表明，在所有类型的接触性运动中，白质稀疏和海马硬化与RHI暴露有关。此外，在美式足球运动员中，这些病理导致了独立于p-tau病理的痴呆。
Characterizing white matter and vascular pathologies in brain donors exposed to repetitive head impacts
Chronic traumatic encephalopathy (CTE) is a progressive brain disease linked to repetitive head impacts (RHI), often incurred from contact sports, and can lead to dementia. Here, we investigated the association between RHI and white matter/vascular neuropathologies and their relative contribution to dementia status in deceased men 50 + years old with and without exposure to RHI from various types of contact and collision sports. Our sample included two RHI groups from the UNITE brain bank: (1) American Football players (RHI-AF, n = 79), and (2) non-AF contact and collision sport athletes (e.g., boxing, rugby; RHI-CCS, n = 49). Controls included similarly aged (± 5 years) male brain donors without RHI. A modified ischemic injury scale (mIIS) served as a global measure of white matter and vascular neuropathologies, encompassing nine subcomponents. Dementia was determined through diagnostic consensus conference based on interviews with families. Using linear regression models controlling for age at death, mIIS was different in RHI-AF versus non-RHI only (p = 0.036). Subsequent logistic regression of each mIIS subcomponent, controlling for age at death, demonstrated that worse white matter rarefaction (RHI-AF; Beta = 1.42, [95% CI 2.03–8.43]; RHI-CCS; Beta = 1.93, [95% CI 2.35–20.17]) and hippocampal sclerosis (RHI-AF; Beta = 2.01, [95% CI 2.69–20.81]; RHI-CCS; Beta = 2.19, [95% CI 2.49–32.10]) was more common in RHI groups from their controls. Further, logistic regressions found that higher global mIIS correlated with increased odds of dementia in only the RHI-AF group (p = 0.02), driven by white matter rarefaction (β = 0.94, [95% CI 1.66–4.00]) and hippocampal sclerosis (β = 1.08, [95% CI 1.35–6.42]). There were similar findings in RHI-CCS group for odds of dementia (p = 0.048), including white matter rarefaction (β = 0.68, [95% CI 1.22–3.21], p = 0.05). Overall, these results demonstrate that white matter rarefaction and hippocampal sclerosis are linked to RHI exposure across all types of contact sports. Further, these pathologies contribute to dementia independent of p-tau pathology in American football players.
期刊介绍：
Acta Neuropathologica publishes top-quality papers on the pathology of neurological diseases and experimental studies on molecular and cellular mechanisms using in vitro and in vivo models, ideally validated by analysis of human tissues. The journal accepts Original Papers, Review Articles, Case Reports, and Scientific Correspondence (Letters). Manuscripts must adhere to ethical standards, including review by appropriate ethics committees for human studies and compliance with principles of laboratory animal care for animal experiments. Failure to comply may result in rejection of the manuscript, and authors are responsible for ensuring accuracy and adherence to these requirements.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
