A longitudinal study of chronic TBI in OEF/OIF/OND Veterans and service members

描述(由申请人提供)： 项目背景/基本原理。约15%的服役人员在参加持久自由行动/伊拉克自由行动/新黎明行动(OEF/OIF/OND)时曾一次或多次遭受创伤性脑损伤(TBI)。众所周知，脑外伤对平民和越南退伍军人的长期影响包括神经退行性疾病。然而，目前对持续冲突期间发生的创伤性脑损伤知之甚少，现在是时候调查爆炸和非爆炸相关脑损伤对OEF/OIF/OND退伍军人和军人的慢性影响。项目目标。这项研究的总体目标是描述OEF/OIF/OND退伍军人和服役人员遭受的脑创伤的慢性影响，具体目标包括评估这些影响对认知、神经状态和功能结果的影响，以及通过多模式脑成像显示的与继发性病理相关的功能结果。相关目标包括研究遗传学、认知储备和大脑储备如何调节脑外伤对预后的慢性影响。项目方法。这项双队列纵向研究将招募200名OEF/OIF/OND退伍军人和服役人员，其中150人报告至少一次脑外伤，50人身体部位除大脑以外受伤或没有受伤。参与者将在迈克尔·E·德·巴基退伍军人事务医疗中心(MEDVAMC)以及位于胡德堡的布鲁克陆军医疗中心(BAMC)和达纳尔陆军医疗中心(DAMC)的协调地点登记。在知情同意和资格筛选之后，受伤后至少两个月的参与者将在MEDVAMC或BAMC/DAMC完成基线面对面评估，其中包括认知测试、功能状态、神经学检查和脑成像。磁共振成像(MRI)将用于评估脑区和总白质体积以及皮质厚度，扩散张量成像(DTI)将检查白质束的微结构完整性，静息状态功能连接性磁共振(FcMRI)将测量脑自发激活，磁共振波谱(MRS)将评估被认为在脑损伤后神经递质水平的变化。抽血将为基因分型提供血清。后续行动将包括在基线后6个月和18个月对认知和功能状态进行基于网络的评估，并在12个月时进行第二次面对面评估，重复基线时进行的结果测量和脑成像。数据将在一个面向对象的数据库中存档，该数据库专为在协作环境中存储和挖掘科学数据而设计。数据管理和统计分析将由MEDVAMC的高级项目统计师与其他研究调查员协调进行。行政监督将由调查员和项目工作人员按其专长和作用分组提供，包括行政、征聘和保留、成像、神经心理评估、神经学检查、遗传学和数据管理/分析。为确保项目地点之间的统一程序，将在头三个月举办一次讲习班，并完成一份项目手册。在两个项目地点对类似的核磁共振扫描仪进行质量保证(QA)测试将确保高质量的图像数据，对认知和行为数据的审计，包括神经心理学家的监测，将为这些措施提供质量保证。与退伍军人管理局健康使命的相关性。OEF/OIF/OND退伍军人和服役人员遭受的单一和重复创伤性脑损伤的慢性影响知之甚少，但可能包括影响退伍军人及其家人长期健康和生活质量的神经退行性疾病。该项目将增强VHA监测和识别脑外伤的后遗症的能力，包括使用先进的脑成像来为康复和保健资源的规划提供信息。 公共卫生相关性： 与战斗相关的颅脑损伤的纵向研究很少，而且调节长期病理和结果的神经机制也很少被理解。确定与战斗有关的创伤性脑损伤的长期影响将为那些担心自己在晚年患上神经退行性疾病的风险的退伍军人提供关键信息，并将为公共政策提供信息，以确保为退伍军人的未来护理提供适当的资源。关于创伤后应激障碍和抑郁症状对脑功能和战斗相关脑损伤后预后的影响，也存在知识差距。此外，这项调查还将阐明宿主因素的潜在作用，如遗传学和认知和大脑储备。这是一个独特的机会，可以利用正在进行的横断面研究的资源，扩大其范围，并将其扩展到纵向设计中。我们预计，这将有助于更好地了解脑外伤，并为开发新的筛查工具和康复程序提供基础。

DESCRIPTION (provided by applicant): Project Background/Rationale. About 15% of service members have sustained a traumatic brain injury (TBI) on one or more occasions while deployed in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND). The long-term effects of TBI in civilians and in Vietnam veterans are known to include neurodegenerative conditions. However, little is currently known about TBI sustained during the ongoing conflicts and it is timely to investigate the chronic effects of blast and non-blast-related TBI in OEF/OIF/OND veterans and service members. Project Objectives. The study's broad objective is to characterize the chronic effects of TBI sustained by OEF/OIF/OND veterans and service members, and the specific aims include the evaluation of these effects on cognition, neurologic status, and functional outcome in relation to secondary pathology shown by multimodality brain imaging. Related objectives include an examination of how genetics, cognitive reserve, and brain reserve moderate the chronic effects of TBI on outcome. Project Methods. This dual cohort, longitudinal study would enroll 200 OEF/OIF/OND veterans and service members, including 150 who reported at least one TBI and 50 with an injury to body regions other than the brain or no injury. Participants would be enrolled at the Michael E. De Bakey Veterans Affairs Medical Center (MEDVAMC) and from a coordinated site at Brooke Army Medical Center (BAMC) and Darnall Army Medical Center (DAMC) at Fort Hood. Following informed consent and screening for eligibility, participants who are least two months post-injury would complete a baseline, in-person assessment at the MEDVAMC or BAMC/DAMC that would include cognitive testing, functional status, neurologic examination, and brain imaging. Magnetic resonance imaging (MRI) would be performed to assess brain region and total white matter volumes and cortical thickness, diffusion tensor imaging (DTI) would examine microstructural integrity of white matter tracts, resting state functional connectivity MRI (fcMRI) would measure spontaneous brain activation, and magnetic resonance spectroscopy (MRS) would assess levels of neurotransmitters that are thought to be altered following TBI. A blood draw would provide serum for genotyping. Follow-ups would include web-based assessment of cognition and functional status at six and 18 months after baseline and a second in-person assessment at 12 months that would repeat the outcomes measurement and brain imaging that had been performed at baseline. Data would be archived in an object-oriented database designed for the storage and mining of scientific data in collaborative environments. Data management and statistical analysis would be performed by the senior project statistician at the MEDVAMC in coordination with the other study investigators. Administrative oversight would be provided by subgroups of investigators and project staff organized by their expertise and roles, including Administration, Recruitment and Retention, Imaging, Neuropsychological Assessment, Neurological Examination, Genetics, and Data Management/Analysis. To ensure uniform procedures between the project sites, a workshop would be held and a project manual completed during the first three months. Quality assurance (QA) testing of the similar MRI scanners at the two project sites would ensure high quality image data and audits of the cognitive and behavioral data, including monitoring by neuropsychologists, would provide QA for those measures. Relevance to the VA Health Mission. The chronic effects of single and repetitive TBI sustained by OEF/OIF/OND veterans and service members are poorly understood, but potentially include neurodegenerative conditions that impact the long-term health and quality of life of veterans and their families. This project would enhance the capability of VHA to monitor and identify late effects of TBI, including the use of advanced brain imaging to inform planning of rehabilitation and healthcare resources. PUBLIC HEALTH RELEVANCE: Longitudinal studies of combat-related TBI are sparse, and the neural mechanisms mediating long-term pathology and outcome are poorly understood. Establishing the long-term effects of combat-related TBI would provide critical information to veterans who are concerned about their own risk for developing neurodegenerative conditions later in life and would inform public policy to ensure that appropriate resources are available for the future care of veterans. There is also a knowledge gap regarding the effects of PTSD and depressive symptoms on brain function and outcome following combat-related TBI. In addition, this investigation will elucidate the potential role of host factors such as genetics and cognitive and brain reserve. This represents a unique opportunity to leverage the resources of ongoing cross-sectional studies, expand their scope, and extend them into a longitudinal design. We anticipate that this will allow a better understanding of TBI and provide the basis for development of new screening tools and rehabilitation procedures.