Longitudinal assessment of Gulf War veterans with suspected Sarin exposure

对疑似接触沙林的海湾战争退伍军人进行纵向评估

• 批准号: 8581089
• 负责人: MICHAEL W WEINER
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581089
• 关键词: Accounting; Acute; Age; Alcohol or Other Drugs use; Alcohols; Alzheimer' s Disease; Anisotropy; Apolipoproteins; Attention; Behavioral; Biological; Brain; California; Cognitive; Complex; Confounding Factors (Epidemiology); Dementia; Department of Defense; Diffusion Magnetic Resonance Imaging; Dose; Education; Exposure to; Genotype; Goals; Gulf War; Health; Hippocampal Formation; Hippocampus (Brain); Hour; Image; Impaired cognition; Iraq; Kansas; Measures; Memory; Military Personnel; Modeling; Nerve Degeneration; Neurodegenerative Disorders; Performance; Post-Traumatic Stress Disorders; Preventive; Questionnaires; Rattus; Reaction Time; Relative (related person); Research; Retrieval; Sampling; Sarin; Severities; Smoking; Subway; Testing; Tokyo; Uncertainty; Verbal Learning; Veterans; age group; attack victim; base; brain volume; cerebral atrophy; cognitive function; cohort; cyclosarin; dentate gyrus; depressive symptoms; experience; gray matter; hippocampal atrophy; improved; indexing; performance tests; public health relevance; sex; stem; white matter

DESCRIPTION (provided by applicant): Despite uncertainty in the Department of Defense (DOD) ''plume'' model assumptions of sarin (GB; o-isopropyl methylphosphonoflouridate) and cyclosarin (GF; cyclohexyl methylphosphonoflouridate) exposure following the destruction of an Iraqi munitions storage complex at Khamisiyah, Iraq during the first Gulf War (GW), we and others have found evidence of brain atrophy in three separate cohorts of GW veterans with suspected exposure at 8-19 years after the incident.[1-3] We believe this makes it the most replicated biological finding in GW veterans to date and worthy of additional research. However, the combined total number of GW veterans with suspected exposure in the past studies (N=130) represents only a tiny fraction of the more than 100,000 GW veterans with suspected GB/GF exposure. Therefore, it is important to confirm and extend the findings of structural and functional brain changes in a larger, non-overlapping sample of GB/GF exposed GW veterans. The goal of this study is to replicate and extend our previous findings of brain atrophy and cognitive impairment in a new sample of 150 GB/GF exposed relative to a new sample of 150 matched non-GB/GF exposed GW veterans. The first aim is to replicate our previous findings of reduced brain volume in GB/GF exposed veterans. Aim 2 will expand our previous finding of hippocampal atrophy in GB/GF exposed veterans by examining the effect of GB/GF exposure on hippocampal subfields. Aim 3 will expand our previous finding of reduced total brain white matter volume in GB/GF-exposed veterans by using diffusion tensor imaging (DTI) to examine the effects of GB/GF exposure on white matter microstructure integrity. Aim 4 will replicate and extend our previous finding of impaired cognitive function (i.e., attention and memory) in GB/GF exposed GW veterans. Exploratory analyses will: 1) examine the relationship between estimated cumulative GB/GF exposure levels, based on the DOD reanalysis of the 2000 plume models using improved meteorological modeling and more accurate estimates of the total number of GB/GF-containing rockets destroyed with measures of brain and hippocampal subfield volumes, DTI indices, and cognitive performance; 2) assess potential differences in wartime experiences between exposed and non-exposed groups using Dr. Lea Steele's Kansas Gulf War Military and Health Questionnaire [4,5] and the relationship between these wartime experiences with measures of brain and hippocampal subfield volumes, DTI values, and cognitive performance. The exposed and unexposed GW veterans will be a priori matched for age, sex, and Gulf War Illness status. We will account for other potentially confounding variables such as years of education, posttraumatic stress disorder and depression symptom severity, smoking, alcohol and non-alcohol substance use, apolipoprotein ¿ 4 genotype, and for analyses of brain volume, intracranial volume as covariates in the statistical analyses. Evidence suggests that reduced brain volume and impaired cognitive function may increase vulnerability to the pathological effects of neurodegenerative disease, such as Alzheimer's disease. Therefore, if we find confirmatory evidence of neurodegeneration and cognitive impairment in yet another cohort of GB/GF exposed GW veterans, this could have implications for the VA to employ non-pharmacological, and pharmacological, when they become available, dementia preventive measures in the treatment of GW veterans with suspected GB/GF exposure as these veterans approach old age.

描述（由申请人提供）： 尽管国防部（DOD）“羽流”模型假设存在不确定性，但在伊拉克哈米西亚的伊拉克弹药储存设施被毁后，沙林（GB；邻异丙基甲基氟化膦）和环沙林（GF；环己基甲基氟化膦）的暴露情况存在不确定性。第一次海湾战争 (GW) 期间，我们和其他人在三组单独的 GW 退伍军人中发现了脑萎缩的证据，这些退伍军人疑似暴露于事件发生后 8-19 年。[1-3] 我们相信，这使其成为迄今为止在 GW 退伍军人中重复最多的生物学发现，值得进行更多研究。但是，在过去的研究中疑似暴露的 GW 退伍军人总数。 (N=130) 仅代表超过 100,000 名疑似 GB/GF 暴露的 GW 退伍军人中的一小部分，因此，在更大的非重叠样本中确认和扩展大脑结构和功能变化的发现非常重要。本研究的目标是在 150 个 GB/GF 暴露的新样本中，相对于 150 个匹配的非 GB/GF 暴露的新样本，复制并扩展我们之前关于脑萎缩和认知障碍的发现。 GW 退伍军人。第一个目标是复制我们在 GB/GF 暴露退伍军人中脑容量减少的发现，目标 2 将通过之前检查 GB/GF 退伍军人的影响来扩展我们之前对 GB/GF 退伍军人海马萎缩的发现。目标 3 将通过使用弥散张量成像 (DTI) 检查 GB/GF 暴露对白质微观结构的影响，扩大我们之前关于 GB/GF 暴露退伍军人大脑白质体积减少的发现。目标 4 将复制并扩展我们之前对 GB/GF 暴露的 GW 退伍军人认知功能受损（即注意力和记忆力）的发现，探索性分析将：1）检查估计累积之间的关系。 GB/GF 暴露水平，基于国防部对 2000 个羽流模型的重新分析，使用改进的气象模型，并通过测量大脑和海马子区域体积、DTI 指数和认知能力，更准确地估计被摧毁的含 GB/GF 的火箭总数2) 使用 Lea Steele 博士的堪萨斯海湾战争军事和健康问卷 [4,5] 评估暴露组和非暴露组之间战时经历的潜在差异以及这些战时经历之间的关系通过测量大脑和海马亚区体积、DTI 值和认知表现，我们将先验地匹配暴露和未暴露的 GW 退伍军人的年龄、性别和海湾战争疾病状况。教育、创伤后应激障碍和抑郁症状严重程度、吸烟、饮酒和非酒精物质使用、载脂蛋白 ¿ 4 基因型，以及脑容量分析，颅内容量作为统计分析中的协变量，证据表明，脑容量减少和认知功能受损可能会增加对神经退行性疾病（例如阿尔茨海默病）病理影响的脆弱性。在另一组暴露于 GB/GF 的 GW 退伍军人中，有确凿证据表明神经退行性变和认知障碍，这可能对退伍军人管理局在可用的非药物和药物预防措施中采用痴呆症预防措施产生影响。 GW 退伍军人随着年事已高，疑似接触过 GB/GF。