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）的沙林“羽流”模型假设存在不确定性，（GB; O-异丙基甲基膦酸酯）和环沙林（GF;在第一次海湾战争期间，伊拉克哈米斯耶的一个伊拉克弹药储存综合设施被摧毁后，我们和其他人在三个不同的GW退伍军人队列中发现了脑萎缩的证据，这些退伍军人在事件发生后8-19年被怀疑接触过。[1-3]我们相信这是迄今为止GW退伍军人中复制最多的生物学发现，值得进一步研究。然而，过去研究中疑似暴露的GW退伍军人总人数（N=130）仅占疑似暴露于GB/GF的100，000多名GW退伍军人的一小部分。因此，在GB/GF暴露的GW退伍军人的较大、非重叠样本中确认和扩展脑结构和功能变化的发现非常重要。本研究的目的是复制和扩展我们以前的研究结果，脑萎缩和认知功能障碍的一个新的样本150 GB/GF暴露相对于一个新的样本150匹配的非GB/GF暴露GW退伍军人。第一个目的是复制我们以前的研究结果，即GB/GF暴露的退伍军人脑容量减少。目的2将通过检查GB/GF暴露对海马亚区的影响来扩展我们先前在GB/GF暴露退伍军人中海马萎缩的发现。目的3将扩大我们以前的发现，减少总脑白色物质体积在GB/GF暴露退伍军人通过使用扩散张量成像（DTI）检查GB/GF暴露对白色物质微结构完整性的影响。目标4将复制和扩展我们先前对认知功能受损的发现（即，注意力和记忆力）。探索性分析将：1）根据国防部对2000年羽流模型的再分析，使用改进的气象模型，以及对销毁的含GB/GF火箭总数的更准确估计，通过测量大脑和海马子域体积、DTI指数和认知能力，检查估计的累积GB/GF暴露水平之间的关系; 2）使用莱亚斯蒂尔博士的堪萨斯海湾战争军事和健康问卷评估暴露组和非暴露组之间战时经历的潜在差异[4，5]以及这些战时经历与脑和海马子区体积、DTI值和认知表现的测量之间的关系。暴露和未暴露的GW退伍军人将在年龄、性别和海湾战争疾病状态方面进行先验匹配。我们将考虑其他潜在的混杂变量，如教育年限、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，并将脑体积、颅内体积分析作为统计分析中的协变量。有证据表明，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（如阿尔茨海默病）病理影响的脆弱性。因此，如果我们在另一个GB/GF暴露GW退伍军人队列中发现神经退行性变和认知障碍的确证性证据，这可能会影响VA在这些退伍军人接近老年时采用非药理学和药理学预防措施治疗疑似GB/GF暴露的GW退伍军人。