VA Biorepository: Gulf War Veterans' Illnesses Biorepository

 描述（由申请人提供）： 在1990-1991年海湾战争期间，在沙漠盾牌和沙漠风暴行动中服役的70万男女中，多达三分之一的人患上了一种称为海湾战争退伍军人病的慢性多系统疾病。神经行为发现包括记忆问题、执行系统缺陷、运动和处理速度减慢、持续注意力缺陷、视觉空间技能降低和精神功能障碍。鉴于上述认知缺陷的范围，结合神经影像学上的结构和功能异常证据，GWVI中可能也发生神经病理学变化。几种环境暴露被认为是GWVI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）农药/神经毒剂（例如，沙林/环沙林）。缺陷的模式可能与GWV是否暴露于OP神经毒剂以及它们的病前脆弱性（例如，PON 1状态）。GWV也可能有更高的风险发展为进行性神经退行性疾病 比如老年痴呆症一些研究表明，加速老化可能发生在GWVI与轴突运输缺陷，增加轴向扩散，增加WM各向异性的扩散张量成像和胰岛素抵抗和/或代谢综合征。GWV中海马体积减少的发现表明，缺陷的模式可能与阿尔茨海默型痴呆的发展一致。这一点很重要，因为GWV群体一般都在老龄化; 52%的GWV年龄在45岁及以上，16%的年龄在55岁至85岁以上。此外，最近的证据表明，出乎意料的大量GW退伍军人遭受创伤性脑损伤（TBI），因此他们也可能有长期后遗症的风险，如慢性创伤性脑病（CTE）。考虑到上述问题，迫切需要一个GWVI CNS组织生物储存库，对登记的GWV进行广泛的生前纵向评估。 我们的第一个具体目标是建立一个VA GWVIB作为一个国家资源，以支持GWRI的病因和发病机制的研究，我们的第二个目标是对注册者进行选定的心理和生物评估，以最大限度地提高捐赠给GWVIB的组织的价值。当结合生前健康数据和生物学评估（如ApoE基因型和血清PON 1活性）时，良好表征的CNS组织将对推进GWVI研究非常宝贵。GWVIB将是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）之间的多站点合作。GWVIB将利用波士顿和图森研究中心在招募、组织收集、处理、储存、神经病理学诊断、医学信息学和数据管理方面的优势。VABHS将作为操作/数据协调中心，进行神经病理学诊断分析，SAVAHCS将在CNS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。值得注意的是，要启动的主动与被动招募方法的利用，扩大我们的组织收集退伍军人控制通过与国家疾病研究交流（NDRI）的合作，并改善推广到研究人员，以增加GWVIB在GWI研究的利用。这将使我们能够利用GWVIB已经到位的VA资源的大量投资，并为现有的临床和CNS组织资源增值。

 DESCRIPTION (provided by applicant): Up to one third of the 700,000 men and women who served in Operations Desert Shield and Desert Storm during the 1990-1991 Gulf War (GW) have developed a chronic multisystem illness known as Gulf War Veterans' Illness (GWVI). 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 cognitive deficits noted above, combined with evidence of structural and functional abnormalities on neuroimaging, it is likely that neuropathological changes also occur in GWVI. Several environmental exposures have been implicated as potential contributors to GWVI 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). The pattern of deficits may be related to whether GWV were exposed to OP nerve agents as well as their premorbid vulnerability (e.g., PON1 status) to such exposures. GWV may also be at higher risk for developing a progressive neurodegenerative disorder such as Alzheimer's Disease as they age. Some studies suggest that accelerated aging may occur in GWVI related to axonal transport deficits, increased axial diffusivity, increased WM anisotropy on diffusion tensor imaging and insulin resistance and/or metabolic syndrome. Findings of reduced hippocampal volume in GWV suggest that that the pattern of deficits may be consistent the development of an Alzheimer-type dementia. This is important to investigate because the GWV cohort in general is aging; 52% of GWV are age 45 and older and 16% are age 55 to 85+. In addition, recent evidence suggests that an unexpectedly large number of GW veterans sustained traumatic brain injuries (TBI) so they may also be at risk for long term sequelae such as chronic traumatic encephalopathy (CTE). Given the issues raised above, there is a critical need for a GWVI CNS tissue biorepository that will conduct extensive ante mortem longitudinal assessments on enrolled GWV. Our first specific aim is to establish a VA GWVIB as a national resource to support research on the etiology and pathogenesis of GWRI and our second aim is to perform selected psychometric and biological assessments on enrollees to maximize the value of tissue donated to the GWVIB. Well-characterized 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 GWVI. The GWVIB will be 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 are the utilization of an active versus passive recruitment approach, enlarging our collection of tissue from Veteran controls through a collaboration with the National Disease Research Interchange (NDRI), and improved outreach to investigators to increase the utilization of the GWVIB in GWI research. This will allow us to leverage the substantial investment of VA resources already in place at GWVIB and to add value to existing clinical and CNS tissue resources.