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: 9890042
• 负责人: Christopher B Brady
• 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/9890042
• 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; 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; 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; 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，已经过去了二十七年。 大约 700,000 名在那场战争中服役的海湾战争退伍军人 (GWV) 现年 45 岁，其中大约一半 超过三分之一的男性年龄在 55 岁及以上。 在二战期间参加“沙漠盾牌”和“沙漠风暴”行动的女性经历了慢性、 多系统疾病统称为海湾战争病 (GWI) 普遍主诉是中枢神经系统疾病。 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、 此外，GWV 的发生率也有所升高。 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 GWV 中可能比之前预想的更为普遍，这可能 增加慢性创伤性脑病（CTE）和痴呆等长期后遗症的风险。 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 速度、持续注意力缺陷、视觉空间技能下降和精神运动功能障碍。 上述缺陷的范围，结合结构和功能异常的证据 神经影像学显示，GWI 中很可能也会发生神经病理学变化。 被认为是 GWI 的潜在因素，包括暴露于乙酰胆碱酯酶 (AChE) 抑制剂，例如溴化吡斯的明（PB；抗神经毒气丸）和有机磷酸酯（OP） 鉴于上述问题，迫切需要一种杀虫剂/神经毒剂（例如沙林/环沙林）。 GWI CNS 死后组织生物样本库将进行广泛的死前纵向评估 我们的第一个具体目标是继续并加强海湾战争。 退伍军人疾病生物存储库 (GWVIB) 作为支持病因学研究的国家资源 GWI 和相关神经系统疾病的发病机制，我们的第二个目标是利用 GWVIB 作为所有 GWI 研究的增值资源，通过从这些研究中共同注册 GWVS 队列并提供长期随访和脑库。 结合生前健康数据和生物学评估（例如 ApoE 基因型和血清 PON1 活动）对于推进 GWI 的研究具有无价的价值。 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)。 GWVIB 将利用波士顿和图森站点在登记、组织采集、处理、 存储、神经病理诊断、医学信息学和数据管理。 操作/数据协调中心并与 SAVAHCS 进行神经病理学诊断分析 SAVAHCS 还将协调中枢神经系统组织，贡献中枢神经系统组织处理和储存方面的专业知识。 本融资周期中要启动的显着改进是利用积极的资金。 招募患有脑癌和与年龄相关的神经退行性疾病的 GWV（以及我们正在进行的 通过我们与 VA 神经肿瘤学和神经病学诊所的合作，招募一般 GWV。 最近与新的大规模国家 GWI 研究开展的合作将提供新的 GWV 队列 有兴趣参与研究，这已被证明可以提高大脑招募的成功率 GWVIB 将与这些 GWI 研究合作，组建 GWI 合作研究网络，以共同 注册 GWV 可以以相对较低的增量成本增强整个 VA GWI 研究组合。