Clinicopathological Correlation in Chronic Traumatic Encephalopathy (CTE) and Chronic Traumatic Brain Injury (cTBI)

慢性创伤性脑病 (CTE) 和慢性创伤性脑损伤 (cTBI) 的临床病理学相关性

• 批准号: 10227043
• 负责人: Jesse Benjamin Mez
• 金额: $ 24.44万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227043
• 关键词: Address; Age; Alzheimer' s disease related dementia; Amyloid beta-Protein; Anatomy; Anxiety; Atrophic; Attention; Behavior; Blinded; Brain; Chronic; Clinical; Clinical Data; Clinical Research; Cognitive; Consensus; Corpus Callosum; Counseling; Craniocerebral Trauma; Data; Data Collection; Deposition; Diagnosis; Diagnostic; Diagnostic Errors; Disease; Elderly; Executive Dysfunction; Family; Family member; Future; Goals; Gold; Image; Impaired cognition; Impairment; Impulsivity; Incidence; Individual; Knowledge; Language; Lesion; Life; MRI Scans; Magnetic Resonance Imaging; Medical Records; Memory; Memory impairment; Mental Depression; Military Personnel; Moods; Motor; Nerve Degeneration; Neurofibrillary Tangles; Neuropsychological Tests; Neuropsychology; Pathologic; Pathology; Pattern; Prevalence; Process; Prognosis; Recording of previous events; Reporting; Research; Research Project Grants; Sampling; Sensitivity and Specificity; Septum Pellucidum; Source; Structure; Syndrome; Testing; Thinness; Traumatic Brain Injury; Validity and Reliability; Visual; Visuospatial; White Matter Hyperintensity; alpha synuclein; base; cerebral atrophy; chronic traumatic encephalopathy; clinical diagnostics; contact sports; density; effective therapy; executive function; head impact; hippocampal atrophy; in vivo; machine learning method; member; mixed dementia; motor symptom; multidisciplinary; neuropathology; predictive modeling; prospective; protein TDP-43; regional atrophy; white matter

Project 2 focuses on the clinical features associated with chronic traumatic encephalopathy (CTE) and chronic traumatic brain injury (cTBI) pathologies. Currently, CTE only can be diagnosed neuropathologically. Diagnosing CTE in life is critical so that incidence and prevalence can be estimated, the course and prognosis can be understood and therapies can be developed. To an even greater extent than CTE, the clinical correlates of cTBI (defined for the purposes of this project as a chronic cavitary lesion after a moderate to severe TBI) are unknown. The overarching hypothesis of this project is that there are distinct mood, behavior, cognitive, motor and imaging features of CTE and cTBI. We will supplement existing clinical and neuropathological data from each of the eight brain banks with newly collected data to address three specific aims. In Aim 1, we will test the validity and reliability of the traumatic encephalopathy syndrome (TES) clinical criteria. These criteria were previously proposed to diagnose CTE in life, but are also meant to capture other TBI-related neurodegenerative processes. From family members of 225 brain donors across a range of ages and TBI, contact and collision sport and military exposures, clinicians will obtain a semi- structured history. A multi-disciplinary expert consensus panel will assess whether TES criteria are met. We will assess inter-rater reliability and sensitivity, specificity and accuracy using first CTE pathology and then cTBI pathology as the gold-standard. In Aim 2, we will use clinical features to construct predictive models of CTE and cTBI pathology. For 1,500 brain donors from across the brain banks, we will use existing data and collect from family members additional extensive structured clinical data, including a variety of cognitive, mood, behavior and motor symptoms. We will use the clinical features to build predictive models of CTE and cTBI pathology using knowledge guided and pure data-driven (machine learning) methodologies. In Aim 3, we will investigate structural MRI and neuropsychological (NP) correlates of CTE and cTBI pathology. For brain donors from across the brain banks, we will compile previously obtained in-vivo brain MRI scans and NP testing. MRIs will be visually rated for regional atrophy, white matter hyperintensities, cavum septum pellucidum, corpus callosum thinning and microhemorrhages. Using NP reports, we will categorize donors based on cognitive and mood/behavior domains with impairment, including memory, executive function, attention, visuospatial function, language, depression and anxiety. We will test associations between CTE and cTBI pathology, MRI visual ratings and patterns of impairment on NP testing. This project will add comprehensive harmonized clinical information to one of the largest brain donor samples with well- characterized histories of RHI and TBI. Findings from this project will help refine existing clinical diagnostic criteria for CTE and inform future clinical diagnostic criteria for cTBI. Diagnosis in life is pivotal to counsel families about disease course and prognosis and to develop effective therapies.

项目2重点关注慢性创伤性脑病（CTE）和慢性脑损伤相关的临床特征。 创伤性脑损伤（cTBI）病理学。目前，CTE只能通过神经病理学诊断。 生活中CTE的诊断至关重要，因此可以估计发病率和患病率， 可以被理解，也可以开发出治疗方法。在比CTE更大的程度上， cTBI的相关因素（本项目定义为中度至中度脑损伤后的慢性空洞性病变） 严重的TBI）未知。这个项目的首要假设是，有不同的情绪，行为， CTE和cTBI的认知、运动和成像特征。我们将补充现有的临床和 来自八个大脑银行中的每一个的神经病理学数据与新收集的数据，以解决三个特定的 目标。目的一：检验创伤性脑病综合征（TES）量表的效度和信度 临床标准。这些标准以前被提出用于诊断生活中的CTE，但也意味着 捕获其他TBI相关的神经退行性过程。来自225名大脑捐赠者的家庭成员， 年龄范围和TBI，接触和碰撞运动和军事暴露，临床医生将获得半- 结构化历史一个多学科专家共识小组将评估工商业污水附加费标准是否得到满足。我们 将使用首个CTE病理学评估评估者间可靠性和敏感性、特异性和准确性，然后 cTBI病理学作为金标准。在目标2中，我们将使用临床特征来构建预测模型 CTE和cTBI的病理学。对于来自各个脑库的1,500名大脑捐赠者，我们将使用现有数据， 并从家庭成员收集额外的广泛的结构化临床数据，包括各种认知， 情绪行为和运动症状我们将使用临床特征来建立CTE的预测模型， 使用知识引导和纯数据驱动（机器学习）方法的cTBI病理学。在目标3中，我们 将研究CTE和cTBI病理学的结构MRI和神经心理学（NP）相关性。为 大脑捐赠者来自整个大脑银行，我们将编译以前获得的体内脑MRI扫描和NP 试验.将目视评定MRI的局部萎缩、白色高信号、腔隔 胼胝体变薄和微囊化。使用NP报告，我们将对捐赠者进行分类 基于认知和情绪/行为领域的障碍，包括记忆，执行功能， 注意力、视觉空间功能、语言、抑郁和焦虑。我们将测试CTE和 cTBI病理学、MRI视觉评级和NP测试的损伤模式。该项目将增加 全面协调的临床信息，以最大的大脑供体样本之一， RHI和TBI的特征性病史。该项目的发现将有助于完善现有的临床诊断 CTE的标准，并为cTBI的未来临床诊断标准提供信息。生活中的诊断是咨询的关键 家庭了解疾病的过程和预后，并制定有效的治疗方法。