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}
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.