VA Biorepository: Gulf War Veterans' Illnesses Biorepository

自1990-1991年海湾战争结束以来，已经过去了27年。中最年轻的一 大约70万参加过那场战争的海湾战争退伍军人（GWV）现已45岁，其中约一半 年龄在55岁及以上。除了常见的与年龄相关的合并症外，多达三分之一的男性和 在GW期间参加沙漠盾牌行动和沙漠风暴行动的妇女经历了慢性， 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（CNS）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，GWVs已被证明具有升高的速率， 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，我们小组和其他波士顿同事最近的轶事证据表明，轻度 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 增加长期后遗症风险，如慢性创伤性脑病（CTE）和痴呆。 神经行为的发现包括记忆问题，执行系统缺陷，运动和处理减慢 速度，持续的注意力缺陷，减少视觉空间技能和心理功能障碍。鉴于 上述缺陷的范围，结合结构和功能异常的证据， 在神经影像学检查中，神经病理学变化也可能发生在GWI中。几种环境暴露 被认为是GWI的潜在贡献者，包括暴露于乙酰胆碱酯酶（AChE） 抑制剂如溴化吡啶斯的明（PB;抗神经毒气药丸）和有机磷（OP） 杀虫剂/神经毒剂（例如，沙林/环沙林）。鉴于上述问题，迫切需要 GWI CNS死后组织生物储存库，将进行广泛的死后纵向评估 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 退伍军人疾病生物储存库（GWVIB）作为支持病因学研究的国家资源 和发病机制的GWI和相关的神经系统疾病，我们的第二个目标是利用 GWVIB作为所有GWI研究的增值资源，通过共同招收GWVS， 队列，并提供长期随访和脑库。充分表征的死后CNS组织 当结合死前健康数据和生物学评估（如ApoE基因型和血清 PON 1活性）将是非常宝贵的，以推进对GWI的研究。GWVIB是一个多站点协作， VA波士顿医疗保健系统（VABHS）和南亚利桑那州VA医疗保健系统（SAVAHCS）。的 GWVIB将利用波士顿和图森研究中心在招募、组织收集、处理、 存储、神经病理学诊断、医学信息学和数据管理。VABHS将作为 操作/数据协调中心，并与SAVAHCS一起进行神经病理学诊断分析 在中枢神经系统组织处理和储存方面提供专业知识。SAVAHCS还将协调CNS组织 分布在本供资周期内将启动的显著增强措施是利用一个活跃的 招募患有脑癌和年龄相关神经退行性疾病的GWV（沿着我们正在进行的 通过我们与VA神经肿瘤学和神经病学诊所的合作，招募GWV。我们 最近开发的与新的大规模国家GWI研究的合作将提供新的GWV队列 有兴趣参与研究，这已被证明可以提高招聘成功的大脑 捐赠。GWVIB将与这些GWI研究合作，形成合作的GWI研究网络， 招募GWVs，以相对较低的增量成本增强VA GWI的整体研究组合。

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.