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

OEF/OIF/OND 退伍军人和现役军人慢性 TBI 的纵向研究

• 批准号: 8485334
• 负责人: Randall S. Scheibel
• 金额: --
• 依托单位: MICHAEL E DEBAKEY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8485334
• 关键词: Accounting; Acids; Affect; Afghanistan; Alleles; Apolipoprotein E; Archives; Behavior assessment; Behavioral; Blast Cell; Blood; Body Regions; Brain; Brain imaging; Brain region; Brain-Derived Neurotrophic Factor; Caring; Catechol O-Methyltransferase; Cerebrum; Choline; Chronic; Cognition; Cognitive; Comorbidity; Conflict (Psychology); Cross-Sectional Studies; DNA Methylation; Data; Development; Diffuse Axonal Injury; Diffusion Magnetic Resonance Imaging; Educational workshop; Eligibility Determination; Enrollment; Ensure; Episodic memory; Evaluation; Exhibits; Family; Freedom; Future; Genes; Genetic; Genotype; Glutamates; Goals; Head and neck structure; Health; Healthcare; Image; Impaired cognition; Individual; Informed Consent; Injury; Integration Host Factors; Investigation; Iraq; Joints; Knowledge; Late Effects; Life; Link; Lipids; Long-Term Effects; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Manuals; Measurement; Measures; Mediating; Medical center; Mental Depression; Methods; Mining; Mission; Monitor; Morbidity - disease rate; N-acetylaspartate; Nerve Degeneration; Nervous System Physiology; Nervous System Trauma; Neurocognitive; Neurologic; Neurologic Examination; Neurological status; Neurotransmitters; Online Systems; Outcome; Participant; Pathology; Pathway interactions; Perforant Pathway; Performance; Persons; Post-Concussion Syndrome; Post-Traumatic Stress Disorders; Procedures; Public Policy; Quality of life; Questionnaires; Recovery; Registries; Rehabilitation therapy; Reporting; Research Personnel; Resources; Rest; Risk; Role; Secondary to; Serum; Services; Severities; Site; Spectrum Analysis; Subgroup; Symptoms; Testing; Thick; Time; Trauma; Traumatic Brain Injury; Veterans; Vietnam; base; cognitive performance; cognitive recovery; cognitive reserve; cognitive task; cognitive testing; cohort; collaborative environment; combat; data management; database design; depressive symptoms; disability; follow-up; functional decline; functional outcomes; functional status; genetic variant; health administration; hippocampal atrophy; longitudinal design; member; methylation pattern; multimodality; neuroimaging; neuromechanism; neuropsychological; operation; promoter; public health relevance; quality assurance; rehabilitation service; screening; tool; two-dimensional; white matter

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.

描述（由申请人提供）： 项目背景/理由。大约 15% 的军人在参与持久自由行动/伊拉克自由行动/新黎明行动 (OEF/OIF/OND) 期间曾遭受过一次或多次创伤性脑损伤 (TBI)。已知 TBI 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持续的 TBI 知之甚少，现在应该及时调查爆炸和非爆炸相关 TBI 对 OEF/OIF/OND 退伍军人和军人的慢性影响。 项目目标。该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 TBI 的慢性影响，具体目标包括评估这些对认知、神经系统状态和与继发性病理学相关的功能结果的影响，多模态脑成像。相关目标包括检查遗传学、认知储备和大脑储备如何缓和 TBI 对结果的慢性影响。 项目方法。这项双队列纵向研究将招募 200 名 OEF/OIF/OND 退伍军人和现役军人，其中 150 名至少报告过一次 TBI 的人，50 名除大脑以外的身体区域受伤或没有受伤的人。参与者将在迈克尔·E·德巴基退伍军人事务医疗中心 (MEDVAMC) 以及胡德堡布鲁克陆军医疗中心 (BAMC) 和达纳尔陆军医疗中心 (DAMC) 的协调地点报名。在知情同意和资格筛选后，受伤后至少两个月的参与者将在 MEDVAMC 或 BAMC/DAMC 完成基线现场评估，其中包括认知测试、功能状态、神经系统检查和脑成像。 磁共振成像 (MRI) 将用于评估大脑区域和总白质体积以及皮质厚度，扩散张量成像 (DTI) 将检查白质束的微观结构完整性，静息状态功能连接 MRI (fcMRI) 将测量自发大脑激活，磁共振波谱（MRS）将评估被认为在 TBI 后发生改变的神经递质水平。抽血可以提供用于基因分型的血清。后续行动将包括基线后 6 个月和 18 个月时基于网络的认知和功能状态评估，以及 12 个月时的第二次现场评估，该评估将重复基线时进行的结果测量和脑成像。数据将存档在面向对象的数据库中，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 的高级项目统计学家与其他研究人员协调进行。 行政监督将由研究人员和项目工作人员按其专业知识和角色组织的小组提供，包括管理、招募和保留、成像、神经心理学评估、神经学检查、遗传学和数据管理/分析。为了确保项目地点之间的程序统一，将在前三个月内举办研讨会并完成项目手册。在两个项目地点对类似 MRI 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核（包括神经心理学家的监测）将为这些措施提供质量保证。 与 VA 健康使命的相关性。 OEF/OIF/OND 退伍军人和服役人员遭受的单次和重复性 TBI 的慢性影响尚不清楚，但可能包括影响退伍军人及其家人的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 TBI 后期影响的能力，包括使用先进的脑成像为康复和医疗资源规划提供信息。 公共卫生相关性： 与战斗相关的 TBI 的纵向研究很少，并且对介导长期病理和结果的神经机制知之甚少。确定与战斗相关的创伤性脑损伤的长期影响将为那些担心自己在以后生活中患上神经退行性疾病的风险的退伍军人提供重要信息，并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 PTSD 和抑郁症状对战斗相关 TBI 后大脑功能和结果的影响也存在知识差距。此外，这项研究还将阐明遗传、认知和大脑储备等宿主因素的潜在作用。 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。我们预计这将有助于更好地了解 TBI，并为开发新的筛查工具和康复程序提供基础。