Magnetic Resonance Spectroscopy as a Biomarker for Chronic Traumatic Encephalopathy

 描述（由申请方提供）：拟议的研究将使用磁共振波谱（MRS）检查慢性创伤性脑病（CTE）高危个体的神经化学和临床特征之间的关系。CTE是一种神经退行性tau蛋白病，据信部分由目前只能通过神经病理学检查诊断的重复头部撞击（RHI）引起。波士顿大学阿尔茨海默病和CTE中心的研究人员发表了CTE临床表现的研究诊断标准，称为创伤性脑病综合征（TES），与生物标志物（当它们可用时）结合使用，用于CTE的体内诊断。根据过去对神经病理学证实的CTE病例的临床表现的研究，TES标准包括四种变体：行为/情绪、认知、混合和痴呆。拟议研究的一个目标是研究基于MRS的神经化学谱，这些谱可能作为CTE的潜在生物标志物，并有助于区分TES表型亚型。 CTE已被提出涉及由于RHI暴露引起的长期神经代谢改变。神经病理学研究支持CTE中的神经代谢破坏，例如轴突和神经元损失以及神经炎症。MRS是一种先进的神经成像工具，可测量神经代谢功能，并在其他神经退行性疾病（例如， 阿尔茨海默病）。拟议导师的试点工作将RHI与前职业运动员的长期神经化学变化联系起来，这表明MRS可以作为CTE的生物标志物。为了测试这种可能性，拟议的研究将检查在CTE的高风险个体MRS和TES之间的关系。拟议的调查将检查NIH资助的DETECT研究中收集的数据。受试者将包括100名前NFL球员，年龄在40-69岁之间，由于基于所打位置和积极的认知，情绪和行为投诉的RHI高暴露史，可能处于CTE的高风险中。将有一个对照组，由30名年龄相同的男性组成，他们没有脑外伤或接触性运动史，并且没有症状。使用针对DETECT进行的广泛神经心理学、神经学和精神病学评价，将所有受试者分类为TES变体。MRS将量化所有受试者的神经化学物质浓度。我们将测试的假设，即前NFL组将表现出异常的神经化学水平相对于控制，将在一个独特的模式，为每个TES的变种。我们还将调查 神经化学与伴随CTE的各种个体认知、行为和情绪症状之间的关联。这项研究的结果将扩大CTE的有限知识，并可能支持MRS作为CTE的潜在生物标志物。鉴于数百万美国人参与接触性运动，以及经历RHI的军事人员，更好地了解CTE并确定在生活中检测这种疾病的生物标志物将对公共卫生产生重大影响，并促进对CTE风险因素，流行病学，预防和治疗的研究。

 DESCRIPTION (provided by applicant): The proposed study will use magnetic resonance spectroscopy (MRS) to examine the relationship between neurochemistry and clinical features in individuals at high-risk for chronic traumatic encephalopathy (CTE). CTE is a neurodegenerative tauopathy believed to be caused, in part, by repetitive head impacts (RHI) that currently can only be diagnosed by neuropathological examination. Investigators at the Boston University Alzheimer's Disease and CTE Center published research diagnostic criteria for the clinical presentation of CTE, known as Traumatic Encephalopathy Syndrome (TES), to be used in conjunction with biomarkers (when they become available) for in vivo diagnosis of CTE. Based on past work on the clinical presentation of neuropathologically-confirmed CTE cases, TES criteria include four variants: Behavioral/Mood, Cognitive, Mixed, and Dementia. A goal of the proposed research is to investigate MRS-based neurochemical profiles that may serve as potential biomarkers for CTE and help differentiate the TES phenotypic subtypes. CTE has been proposed to involve prolonged neurometabolic alterations due to RHI exposure. Neuropathological research supports neurometabolic disruption in CTE, such as axonal and neuronal loss, and neuroinflammation. MRS, an advanced neuroimaging tool, measures neurometabolic function and has strong clinical utility in other neurodegenerative illnesses (e.g., Alzheimer's disease). Pilot work by proposed mentors has linked RHI with long-term neurochemical changes in former professional athletes, suggesting MRS may serve as a biomarker for CTE. To test this possibility, the proposed study will examine the relationship between MRS and TES in individuals at high-risk for CTE. The proposed investigation will examine data collected in the NIH-funded DETECT study. Subjects will include 100 former NFL players, aged 40-69 years, presumably at high risk for CTE due to a history of high exposure to RHI based on positions played and active cognitive, mood, and behavioral complaints. There will be a control group of 30 same-aged males without history of brain trauma or contact sport involvement, and are asymptomatic. All subjects will be classified into the TES variants using the extensive neuropsychological, neurological, and psychiatric evaluations conducted for DETECT. MRS will quantify neurochemical concentrations for all subjects. We will test the hypothesis that the former NFL group will exhibit abnormal neurochemical levels relative to controls that will present in a distinct pattern for each TES variant. We will also investigate the association between neurochemistry and the various individual cognitive, behavioral, and mood symptoms that accompany CTE. Findings from this study will expand the limited knowledge of CTE and may support MRS as a potential biomarker for CTE. Given the millions of Americans involved in contact sports, as well as military personnel who experience RHI, a better understanding of CTE and identification of biomarkers that detect this disease during life will have a major public health impact and facilitate research into risk factors, epidemiology, prevention, and treatment of CTE.