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”模型的不确定性是对沙林（GB; o-异丙基甲基磷磷酸酯）和环糖素（GF;环己基甲基磷酸膨胀）暴露的暴露，但在伊拉克族储存复杂事物的其他迹象之后，在Khamisiah，Ghamisiah werf First and Gulaf the of tosclohecyl甲基磷酸磷酸磷酸酯）。事件发生后8-19年，三个单独的GW退伍军人同类中的脑萎缩。[1-3]我们认为，这使其成为迄今为止GW退伍军人中最复制的生物学发现，值得进行其他研究。但是，过去研究中怀疑暴露的GW退伍军人总数（n = 130）仅代表超过100,000 GW退伍军人的一小部分，可疑GB/GF暴露。因此，重要的是要确认和扩展较大的，非重叠的GB/GF暴露GW退伍军人样本中结构和功能性大脑变化的发现。这项研究的目的是在150 GB/gf的新样本中相对于150个匹配的非GB/GF暴露的GW退伍军人，在150 GB/GF暴露的新样本中复制和扩展了我们先前对脑萎缩和认知障碍的发现。 AIM 2通过检查GB/GF暴露对海马子场的影响，将扩大我们以前对GB/GF暴露退伍军人中海马萎缩的发现。 AIM 3通过使用扩散张量成像（DTI）来检查GB/GF暴露对白质微观结构完整性的影响，AIM 3将扩大我们先前对GB/GF暴露退伍军人中脑白质体积减少的发现。 AIM 4将复制并扩展我们先前对GB/GF暴露GW退伍军人的认知功能（即注意和记忆）受损的发现。探索性分析将：1）基于对2000年李子模型的DOD重新分析，使用改进的气象模型和更准确的估计值对GB/GF/GF含量的火箭的总估计来检查估计的GB/GF暴露水平之间的关系，并通过大脑和海马子领域的DTI，DTI Indices和dti Indices和coccends concence; 2）使用Lea Steele的堪萨斯州海湾战争军事和健康问卷[4,5]评估暴露与非暴露群体之间战时经历的潜在差异，以及这些战时经验与大脑和海马子场量，DTI值，DTI值和认知性能之间的关系。暴露和意外的GW退伍军人将是年龄，性别和海湾战争疾病状况的先验匹配。我们将考虑其他潜在的混杂变量，例如多年的教育，创伤后应激障碍和抑郁症的抑郁症，吸烟，酒精和非酒精药物的使用，载脂蛋白»4基因型以及用于统计分析中的脑内体积，颅内体积作为协方差的分析。证据表明，脑量减少和认知功能受损可能会增加对神经退行性疾病（例如阿尔茨海默氏病）病理影响的脆弱性。因此，如果我们在另一批GB/GF中发现了神经退行性和认知障碍的证据证据，这可能会影响VA对员工的非药物学和药物的影响，当它们可用时，痴呆症预防性的预防措施在怀疑的GB/GF epposeplose epposeip的痴呆症治疗中，如这些Veterans的年龄。