VA Biorepository: Gulf War Veterans' Illnesses Biorepository

VA 生物储存库：海湾战争退伍军人疾病生物储存库

• 批准号: 10515289
• 负责人: BERTRAND R HUBER
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515289
• 关键词: Acetylcholinesterase Inhibitors; Address; Affect; Age; Age Factors; Aging; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Anisotropy; Apolipoprotein E; Arizona; Arylesterase; Attentional deficit; Autopsy; Axonal Transport; Biological; Boston; Brain; Brain Injuries; Brain scan; Bromides; Cessation of life; Chronic; Chronic Disease; Clinic; Collaborations; Data; Data Coordinating Center; Dementia; Development; Diagnosis; Diagnostic; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Drug or chemical Tissue Distribution; Enrollment; Environmental Exposure; Etiology; Exhibits; Exposure to; Fatigue; Functional disorder; Funding; Genetic; Genomics; Genotype; Gulf War; Gulf War veteran; Healthcare Systems; Hippocampus (Brain); Human; Immune System Diseases; Insulin Resistance; Iraq; Long-Term Effects; Longterm Follow-up; Malignant neoplasm of brain; Medical Informatics; Memory; Metabolic syndrome; Migraine; Modeling; Motor; Musculoskeletal Pain; Nervous System Physiology; Neuralgia; Neuraxis; Neuritis; Neurocognitive Deficit; Neurodegenerative Disorders; Neurology; Organism; Organophosphates; Pathogenesis; Pattern; Persian Gulf Syndrome; Pesticides; Positioning Attribute; Post-Traumatic Stress Disorders; Proteomics; Recovery; Recruitment Activity; Research; Research Personnel; Research Support; Resources; Respiratory Signs and Symptoms; Risk; Sarin; Scientist; Serum; Site; Skin; Stroke; Structure; Symptoms; System; Thinking; Tissue Banks; Tissues; Toxic Environmental Substances; Veterans; Visuospatial; War; Woman; age related; age related neurodegeneration; aging brain; biobank; brain abnormalities; brain tissue; chronic traumatic encephalopathy; cohort; comorbidity; cost; cyclosarin; data management; effective therapy; experience; gastrointestinal; health data; high risk; improved; induced pluripotent stem cell; interest; long-term sequelae; men; mild cognitive impairment; mild traumatic brain injury; mouse model; nerve agent; nerve gas; nervous system disorder; neuro-oncology; neurobehavioral; neuroimaging; neuropathology; neuropsychiatry; operation; pill; processing speed; pyridostigmine; recruit; research study; service member; skills; success; sustained attention; tissue processing; white matter

Twenty-seven years have passed since the end of the 1990-1991 Gulf War (GW). The youngest of the approximately 700,000 Gulf War Veterans (GWV) who served in that war are now 45 years old and about half are age 55 and older. In addition to the usual age-related comorbidities, as many as one third of the men and women who served in Operations Desert Shield and Desert Storm during the GW have experienced chronic, multisystem illnesses collectively known as Gulf War Illness (GWI). Prevalent complaints are central nervous system (CNS) dysfunction, musculoskeletal pain, fatigue, respiratory symptoms, gastrointestinal issues, immunological dysfunction, and skin problems. Furthermore, GWVs have been shown to have elevated rates of brain cancer, amyotrophic lateral sclerosis (ALS), stroke, migraine headaches, neuralgia and neuritis. Additionally, recent anecdotal evidence from our group and other Boston colleagues suggests that mild traumatic brain injuries (mTBI) may be more prevalent in GWVs than previously appreciated, which may increase risk for long term sequelae such as chronic traumatic encephalopathy (CTE) and dementia. Neurobehavioral findings include memory problems, executive system deficits, slowed motor and processing speeds, sustained attention deficits, reduced visuospatial skills and psychomotor dysfunction. Given the spectrum of deficits noted above, combined with evidence of structural and functional abnormalities on neuroimaging, it is likely that neuropathological changes also occur in GWI. Several environmental exposures have been implicated as potential contributors to GWI including exposure to acetylcholinesterase (AChE) inhibitors such as pyridostigmine bromide (PB; anti-nerve gas pills) and organophosphate (OP) pesticides/nerve agents (e.g., sarin/cyclosarin). Given the issues raised above, there is a critical need for a GWI CNS postmortem tissue biorepository that will conduct extensive ante mortem longitudinal assessments on GWVs enrolled prior to their passing. Our first specific aim is to continue and enhance the Gulf War Veterans’ Illnesses Biorepository (GWVIB) as a national resource to support research on the etiology and pathogenesis of GWI and associated neurological disorders, and our second aim is to leverage the GWVIB as a value-added resource for all GWI research studies by co-enrolling GWVS from these cohorts and providing long term follow up and brain banking. Well-characterized postmortem CNS tissue when combined with antemortem health data and biological assessments (such as ApoE genotype and serum PON1 activity) will be invaluable to advance research on GWI. The GWVIB is a multi-site collaboration among VA Boston Healthcare System (VABHS) and the Southern Arizona VA Healthcare System (SAVAHCS). The GWVIB will utilize strengths across the Boston and Tucson sites in enrollment, tissue collection, processing, storage, neuropathological diagnosis, medical informatics and data management. VABHS will serve as the operations/data coordinating center and conduct the neuropathological diagnostic analyses, with SAVAHCS contributing expertise in CNS tissue processing and storage. SAVAHCS will also coordinate CNS tissue distribution. Notable enhancements to be initiated in this funding cycle are the utilization of an active recruitment of GWVs with brain cancer and age-related neurodegenerative disorders (along with our ongoing recruitment of GWVs in general) via our collaboration with VA neuro-oncology and neurology clinics. Our recently developed collaboration with new large scale national GWI studies will provide new cohorts of GWVs interested in participating in research, which has been shown to improve recruitment success for brain donation. The GWVIB will partner with these GWI studies to form collaborative GWI research networks to co- enroll GWVs to enhance the overall VA GWI research portfolio at a relatively low incremental cost.

自1990-1991年海湾战争(GW)结束以来，已经过去了27年。世界上最年轻的 在那次战争中服役的大约70万海湾战争退伍军人(GWV)现在45岁，大约一半 年龄在55岁及以上。除了常见的与年龄有关的并发症外，多达三分之一的男性和 在二战期间在沙漠盾牌和沙漠风暴行动中服役的女性经历了慢性， 多系统疾病统称为海湾战争病(GWI)。常见的主诉是中枢神经系统 中枢神经系统功能障碍、肌肉骨骼疼痛、疲劳、呼吸道症状、胃肠道问题、 免疫功能障碍和皮肤问题。此外，GWV已被证明具有更高的比率 这些疾病包括脑癌、肌萎缩侧索硬化症(ALS)、中风、偏头痛、神经痛和神经炎。 此外，最近来自我们团队和其他波士顿同事的轶事证据表明，轻微的 创伤性脑损伤(MTBI)在GWVS中可能比以前认识到的更普遍，这可能 增加慢性创伤性脑病(CTE)和痴呆症等长期后遗症的风险。 神经行为表现包括记忆问题、执行系统缺陷、运动和处理速度减慢 速度、持续注意力缺陷、视觉空间技能下降和精神运动障碍。给定 上述缺陷的范围，结合结构和功能异常的证据 神经影像，很可能GWI也会出现神经病变。几次环境暴露 被认为是GWI的潜在致病因素，包括接触乙酰胆碱酯酶(AChE) 溴化吡斯的明(PB；抗神经毒气丸)和有机磷(OP)等抑制剂 杀虫剂/神经毒剂(例如沙林/环沙林)。鉴于上述提出的问题，迫切需要一种 GWI CNS死后组织生物库，将进行广泛的宰前纵向评估 在他们通过之前登记的GWVS。我们的第一个具体目标是继续和加强海湾战争 作为支持病因学研究的国家资源的退伍军人疾病生物库(GWVIB) 和发病机制，以及相关的神经疾病，我们的第二个目标是利用 GWVIB作为所有GWI研究的增值资源，通过联合登记以下GWVS 并提供长期随访和人才库。具有良好特征的死后中枢神经系统组织 结合生前健康数据和生物学评估(如载脂蛋白E基因和血清 PON1活动)对推进全球水资源研究将是非常宝贵的。GWVIB是多个站点之间的协作 弗吉尼亚州波士顿医疗保健系统(VABHS)和南亚利桑那州退伍军人医疗保健系统(SAVAHCS)。这个 GWVIB将利用波士顿和图森两个地点在登记、组织收集、处理、 存储、神经病理诊断、医学信息学和数据管理。VABHS将作为 运营/数据协调中心，并使用SAVAHCS进行神经病理诊断分析 在中枢神经系统组织处理和储存方面贡献专业知识。SAVAHCS还将协调CNS组织 分发。在本供资周期中将启动的显著增强措施是利用主动 招募患有脑癌和年龄相关神经退行性疾病的GWV(与我们正在进行的 通过我们与退伍军人事务部神经肿瘤学和神经病学诊所的合作，招募GWV。我们的 最近开发的与新的大规模国家GWI研究的合作将提供新的GWVS队列 对参与研究感兴趣，这已被证明可以提高Brain的招聘成功率 捐款。GWVIB将与这些全球倡议研究合作，形成合作的全球倡议研究网络，以共同 加入GWVS，以相对较低的增量成本增强整个VA GWI研究组合。