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: 9402030
• 负责人: Neil W. Kowall
• 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 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9402030
• 关键词: Acetylcholinesterase Inhibitors; Affect; Age; Aging; Alzheimer' s Disease; Amyloid beta-Protein; Animal Model; Anisotropy; Apolipoprotein E; Arizona; Arylesterase; Assessment tool; Attention; Attentional deficit; Autopsy; Axonal Transport; Biological; Boston; Brain; Brain Injuries; Brain scan; Bromides; Cessation of life; Chronic; Chronic Disease; Clinical; Cognitive; Cognitive deficits; Collaborations; Computerized Medical Record; Data; Data Coordinating Center; Development; Diagnosis; Diagnostic; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Drug or chemical Tissue Distribution; Enrollment; Environmental Exposure; Enzymes; Etiology; Exposure to; Functional disorder; Funding; Future; Genetic; Genotype; Gulf War; Health; Healthcare Systems; Hippocampus (Brain); Human; Insulin Resistance; Intravenous; Investments; Long-Term Effects; Measures; Medical Informatics; Memory; Metabolic syndrome; Metabolism; Motor; Neurocognitive Deficit; Neurodegenerative Disorders; Organophosphates; Participant; Pathogenesis; Patients; Pattern; Pesticides; Pilot Projects; Psychometrics; Questionnaires; Reporting; Research; Research Infrastructure; Research Personnel; Research Support; Resources; Risk; Sarin; Scientist; Serum; Site; Structure; Symptoms; System; Telephone; Telephone Interviews; Thinking; Tissue Banks; Tissues; Toxic Environmental Substances; Traumatic Brain Injury; Variant; Veterans; Visuospatial; Woman; aging brain; biobank; brain abnormalities; brain tissue; chronic traumatic encephalopathy; cognitive testing; cohort; cyclosarin; data management; effective therapy; experience; follow-up; frontal lobe; health data; high risk; improved; men; mild cognitive impairment; mortality; nerve agent; nerve gas; neurobehavioral; neuroimaging; operation; outreach; pill; processing speed; prophylactic; public health relevance; pyridostigmine; recruit; service member; skills; sustained attention; tissue processing; tissue resource; web site

 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.

 描述（由申请人提供）： 1990-1991 年海湾战争 (GW) 期间，参加沙漠盾牌行动和沙漠风暴行动的 70 万名男女军人中，多达三分之一患有慢性多系统疾病，称为海湾战争退伍军人病 (GWVI)，神经行为症状包括记忆障碍。问题、执行系统缺陷、运动和处理速度减慢、持续注意力缺陷、视觉空间技能下降和精神运动功能障碍。根据神经影像学结构和功能异常的证据，GWVI 中也可能发生神经病理学变化，多种环境暴露被认为是 GWVI 的潜在因素，包括暴露于乙酰胆碱酯酶 (AChE) 抑制剂，如溴吡斯的明 (PB；抗神经药物)。毒气丸）和有机磷（OP）杀虫剂/神经毒剂（例如沙林/环沙林）。与 GWV 是否接触过 OP 神经毒剂以及其病前对此类接触的脆弱性（例如 PON1 状态）有关，GWV 也可能面临更高的发展为进行性神经退行性疾病的风险。 一些研究表明，GWVI 的加速衰老可能与轴突运输缺陷、轴向扩散性增加、扩散张量成像的 WM 各向异性增加以及胰岛素抵抗和/或代谢综合征有关。 GWV 表明，缺陷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 队列总体上正在老龄化；52% 的 GWV 正在老龄化。年龄在 45 岁及以上，16% 年龄在 55 岁至 85 岁以上。此外，最近的证据表明，出乎意料地大量的 GW 退伍军人遭受了创伤性脑损伤 (TBI)，因此他们也可能面临长期后遗症的风险，例如慢性创伤性脑损伤。鉴于上述问题，迫切需要 GWVI CNS 组织生物库对登记的 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 VA GWVIB 作为国家资源，以支持 GWRI 的病因学和发病机制研究，我们的第二个目标是对参与者进行选定的心理测量和生物学评估，以最大限度地提高捐赠给 GWVIB Well 的组织的价值。 - 结合生前健康数据和生物学评估（例如 ApoE 基因型和血清 PON1 活性）的中枢神经系统组织特征对于推进 GWVI 的研究具有不可估量的作用。 VA 波士顿医疗系统 (VABHS) 和南亚利桑那州 VA 医疗系统 (SAVAHCS) 之间的合作将利用波士顿和图森站点在登记、组织采集、处理、存储、神经病理学诊断、医疗信息学和数据管理方面的优势。 VABHS 将作为操作/数据协调中心并进行神经病理学诊断分析，SAVAHCS 还将提供中枢神经系统组织处理和存储方面的专业知识，协调中枢神经系统组织的分布。即将启动的增强措施是利用主动与被动招募方法，通过与国家疾病研究交换中心 (NDRI) 合作，扩大我们从退伍军人对照中收集的组织，并改善与研究人员的联系，以提高 GWVIB 在 GWI 中的利用率这将使我们能够利用 GWVIB 现有的 VA 资源的大量投资，并为现有的临床和 CNS 组织资源增加价值。