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

基本信息

批准号：
9914712
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
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9914712
关键词：
Address Age Alzheimer&apos 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 Machine Learning Magnetic Resonance Imaging Medical Records Memory Memory impairment Mental Depression Methodology Military Personnel Moods Motor Nerve Degeneration Neurofibrillary Tangles Neuropsychological Tests Neuropsychology Pathologic Pathology Pattern Prevalence Process Recording of previous events Reporting Research Research Project Grants Sampling Sensitivity and Specificity Septum Pellucidum Source Sports 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 density effective therapy executive function head impact hippocampal atrophy in vivo member mixed dementia motor symptom multidisciplinary neuropathology outcome forecast predictive modeling prospective protein TDP-43 regional atrophy white matter

项目摘要

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 重点关注与慢性创伤性脑病 (CTE) 和慢性创伤性脑病相关的临床特征创伤性脑损伤（cTBI）病理。目前，CTE 只能通过神经病理学来诊断。在生活中诊断 CTE 至关重要，以便可以估计发病率和患病率、病程和预后可以被理解并且可以开发治疗方法。在比 CTE 更大的程度上，临床 cTBI 的相关性（为本项目的目的定义为中度至中度损伤后的慢性空洞病变）严重 TBI）未知。该项目的总体假设是，存在不同的情绪、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脑库中每一个的神经病理学数据以及新收集的数据，以解决三个特定问题目标。在目标 1 中，我们将测试创伤性脑病综合征 (TES) 的有效性和可靠性临床标准。这些标准之前被提出用于诊断生活中的 CTE，但也旨在捕捉其他与 TBI 相关的神经退行性过程。来自 225 名脑捐献者的家庭成员年龄范围和 TBI、接触和碰撞运动以及军事暴露，临床医生将获得半结构化的历史。多学科专家共识小组将评估是否满足 TES 标准。我们将首先使用 CTE 病理学评估评估者间的可靠性和敏感性、特异性和准确性，然后 cTBI 病理学作为金标准。在目标 2 中，我们将利用临床特征构建预测模型 CTE 和 cTBI 病理学。对于来自各个脑库的 1,500 名脑捐献者，我们将使用现有数据并从家庭成员那里收集更多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。我们将利用临床特征建立 CTE 的预测模型 cTBI 病理学使用知识引导和纯数据驱动（机器学习）方法。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。为了来自各个脑库的脑捐赠者，我们将编译之前获得的体内脑 MRI 扫描和 NP 测试。 MRI 将通过肉眼评估区域萎缩、白质高信号、腔间隔透明膜、胼胝体变薄和微出血。使用 NP 报告，我们将对捐赠者进行分类基于有损伤的认知和情绪/行为领域，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 测试损伤模式。该项目将添加将全面协调的临床信息提供给最大的大脑捐赠样本之一，并且具有良好的 RHI 和 TBI 病史的特征。该项目的研究结果将有助于完善现有的临床诊断 CTE 的标准并为未来的 cTBI 临床诊断标准提供信息。生活中的诊断对于咨询至关重要家庭成员了解病程和预后并制定有效的治疗方法。