Chronic Traumatic Encephalopathy: Detection, Diagnosis, Course, and Risk Factors

慢性创伤性脑病：检测、诊断、病程和危险因素

基本信息

批准号：
8960576
负责人：
JEFFREY L. CUMMINGS
金额：
$ 257.4万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-15 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8960576
关键词：
Address Age Alzheimer&apos s Disease Amygdaloid structure Amyloid Astrocytes Attention Award Behavior Behavioral Biological Markers Boxing Brain Brain Chemistry Case Study Clinical Cognitive Consensus Consensus Workshop Control Groups Corpus Callosum Country Data Databases Degenerative Disorder Dementia Deposition Detection Diagnosis Diagnostic Diffusion Magnetic Resonance Imaging Disease Epilepsy Exposure to Frequencies Functional Magnetic Resonance Imaging Genetic Genetic Polymorphism Gold Grant Growth Head Health Image Impairment Individual Intervention Life Liquid substance Literature Longitudinal Studies Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manufactured football Measures Methods Military Personnel Modeling Moods Motor Multicenter Studies Nerve Degeneration Neurocognitive Neurodegenerative Disorders Neurologic Neurons Pattern Plasma Play Positron-Emission Tomography Prevention Process Proxy Publishing Recording of previous events Reporting Research Personnel Rest Risk Risk Factors Science Septum Pellucidum Services Signs and Symptoms Sports Subgroup Symptoms Syndrome Tauopathies Testing Tracer Trauma Traumatic Brain Injury Validation Validity and Reliability Variant Writing Youth chronic traumatic encephalopathy clinical Diagnosis college data sharing design diagnostic accuracy effective intervention experience follow-up head impact high risk high school in vivo infancy insight member men multidisciplinary neuroimaging neuropathology novel physical abuse symposium tau Proteins tau-1 tool uptake white matter

项目摘要

DESCRIPTION (provided by applicant): Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by a distinct deposition of an abnormal form of the tau protein in a pattern that is unique from other diseases, including Alzheimer's disease (AD). CTE has been found most often in professional contact sport athletes (e.g., boxing, football) who have been subjected to repetitive blows to the head resulting in concussive and subconcussive trauma. Neuropathologically-confirmed CTE has been reported in individuals as young as 17 and in athletes who only played sports through high school or college. It also has been found in non-athletes who experienced repetitive head impacts, including epileptics, victims of physical abuse, and military service members. In contrast to what may be inferred by the extensive media attention on CTE, the science of CTE remains in its infancy; critical questions remain, such as whether or not it is a common disease. Although the neuropathological features of CTE have become further clarified in recent years, the clinical presentation of CTE is still not well characterized, even though there have been case reports in the literature of "dementia pugilistica" in boxers since the early 1900's. Clinical diagnostic criteria have only recently been published and lack validation. Neuroimaging and fluid biomarkers developed for the diagnosis of other neurodegenerative diseases have only been used in preliminary studies. There is thus an urgent need to develop accurate methods for detecting and diagnosing CTE during life so that effective interventions for prevention and treatment can be developed. Moreover, though a history of repetitive head impacts is a necessary risk factor for CTE, it alone is not sufficient. There is a need to understand what specific aspects of the head impact exposure places an individual at increased risk for CTE and to examine potential genetic modifiers of that risk. To address these needs, we propose a multidisciplinary, multicenter, longitudinal study of former athletes with high exposure to repetitive head impacts (120 former NFL players with and without symptoms) or medium exposure to repetitive head impact (60 former college football players with and without symptoms) and a control group of 60 asymptomatic same-age men without any history of repetitive head impact exposure or traumatic brain injury. The aims of our proposal are: (1) to collect and analyze neuroimaging and fluid biomarkers for the detection of CTE during life, including the use of a novel PET tracer to measure the amount of abnormal brain tau; (2) to characterize the clinical presentation of CTE; (3) to examine the progression of CTE over a three year period; (4) to refine and validate diagnostic criteria for the clinical diagnosisof CTE; (5) to investigate genetic and head impact exposure risk factors for CTE; and (6) to share project data with researchers across the country and abroad in order to expedite growth in our understanding and treatment of this disease.

描述（由申请人提供）：慢性创伤性脑病（CTE）是一种神经退行性疾病，其特征是异常形式的 tau 蛋白明显沉积，其模式不同于其他疾病，包括阿尔茨海默病（AD）。最常见于职业接触运动运动员（例如拳击、足球），他们的头部受到反复打击，导致脑震荡和亚脑震荡创伤。据报道，经神经病理学证实的 CTE 发生在年仅 17 岁的个体以及仅在高中或大学参加过体育运动的运动员中，在经历过重复性头部撞击的非运动员中也发现了这种情况，包括癫痫患者、身体虐待的受害者和其他人。与媒体对 CTE 的广泛关注所推断的相反，CTE 的科学仍处于起步阶段，例如它是否是一种常见疾病，尽管它具有神经病理学特征。近年来，CTE 的定义已得到进一步明确，尽管自 1900 年代初以来文献中已有拳击手“拳击手痴呆”的病例报告，但 CTE 的临床表现仍不明确。临床诊断标准直到最近才被确定。用于诊断其他神经退行性疾病的神经影像和液体生物标志物仅用于初步研究，因此迫切需要开发准确的方法来检测和诊断生命中的 CTE，以便采取有效的干预措施进行预防和治疗。此外，尽管重复性头部撞击史是 CTE 的一个必要风险因素，但仅凭这一点还不够，需要了解头部撞击暴露的哪些具体方面会增加个体发生 CTE 的风险。检查潜在的遗传为了满足这些需求，我们建议对经常遭受头部重复撞击的前运动员（120 名有或没有症状的前 NFL 球员）或中度遭受重复头部撞击的运动员（60 名前大学运动员）进行一项多学科、多中心的纵向研究。对照组包括 60 名无症状的同龄男性，没有任何重复性头部撞击暴露或创伤性脑损伤史。我们建议的目的是：(1) 收集和分析神经影像和液体生物标志物。这检测生命期间的 CTE，包括使用新型 PET 示踪剂来测量异常脑 tau 的数量；(2) 表征 CTE 的临床表现；(3) 检查三年内 CTE 的进展情况； 4）完善和验证CTE临床诊断的诊断标准；（5）研究CTE的遗传和头部撞击暴露风险因素；（6）与国内外研究人员共享项目数据，以加快CTE的发展；我们对此的理解和处理疾病。