Impact of Combat Exposure on Structural and Functional Brain Connectivity and Risk forAlzheimer's Disease in Aging Veterans

战斗暴露对老年退伍军人大脑结构和功能连接以及阿尔茨海默病风险的影响

• 批准号: 10364388
• 负责人: DAVID H SALAT
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364388
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Amygdaloid structure; Amyloid; Behavioral; Biological; Biological Markers; Body mass index; Boston; Brain; Brain imaging; Caring; Center for Translational Science Activities; Cognition Disorders; Cognitive; Cohort Studies; Data; Dementia; Deterioration; Diabetes Mellitus; Disease; Elderly; Equipment and supply inventories; Exposure to; Funding; Generations; Health; Health Care Costs; Healthcare Systems; Hypertension; Impaired cognition; Impairment; Lead; Life Style; Link; Maps; Measures; Mediator of activation protein; Medical; Memory; Military Personnel; Modeling; Nerve Degeneration; Participant; Pathology; Pathway Analysis; Physiological; Post-Traumatic Stress Disorders; Prevalence; Preventive measure; Principal Investigator; Procedures; Proxy; Rest; Risk; Risk Factors; Sampling; Statistical Models; Stress; Structure; Symptoms; System; Testing; Trauma; Veterans; Visit; Waxes; Work; aged; associated symptom; cognitive development; cognitive function; cognitive performance; cognitive reserve; cohort; combat; disorder risk; emerging adult; follow-up; functional independence; hypercholesterolemia; insight; mild traumatic brain injury; military service; military trauma; military veteran; multimodality; nervous system disorder; neural circuit; neuroimaging; neuromechanism; non-demented; relating to nervous system; resilience; serial imaging; societal costs; stress disorder; support network; tau Proteins; trend; white matter; young adult

Military service in young adulthood is typically accompanied by a variety of combat exposures that are known to increase the risk for cognitive impairment and Alzheimer’s disease (AD) in later life (e.g. hypertension, diabetes, hypercholesterolemia, and body mass index). Although the significant healthcare and societal costs of combat exposure are well documented, it is possible that these primary young adulthood exposures additionally promote later life secondary conditions that are only now being uncovered. Identification of factors that contribute to advanced risk for diseases of aging in older Veterans provides the opportunity to test and initiate treatments that may slow progression of these conditions. Additionally, these data could be used to inform care for the younger, current generation of veterans, including the initiation of lifestyle and medical changes that may ameliorate progression of conditions that promote later life cognitive and behavioral conditions. It is possible that combat-exposure in young adulthood initiates a trajectory of ‘unhealthy aging’ with progressive elevation in biological risk that promotes aging-related neural ‘disconnection’ of structural and functional brain networks. However, limited work to date has been performed linking young adulthood combat exposure to alterations in neural structure and function in older Veterans. Additionally, whether combat- exposure in young adulthood is related to the accumulation of late life biomarker hallmarks of AD, known as the amyloid, tau, neurodegeneration (A-T-N) framework, is currently unknown. Thus, intermediary mechanisms linking young adulthood combat exposure to late life risk must be examined. In the large Translational Research Center for TBI and Stress Disorders (TRACTS) cohort study, we find that younger Veterans with combat exposures and symptoms additionally 1) have elevations in systemic biological risk; 2) show alterations in critical brain network circuitry such as amygdala and default mode network (DMN); and 3) show accelerated aging trends in structural connectivity and white matter microstructure. We aim to conceptually link these findings in the proposed work. We propose that late life risk is conferred first through elevation in systemic health conditions starting in young adulthood (i.e. ‘cumulative biological risk’) that lead to damage to critical brain connections. Combined effects of cumulative biological risk accelerate the deterioration of structural and functional brain networks that support higher cognitive function, including memory systems and/or compensatory systems that provide cognitive reserve in the face of AD pathology. We will test a model of combat-associated amygdala network dysregulation promoting systemic health risk in young adulthood. This cumulative biological risk in turn contributes to neural and cognitive deterioration that is pronounced in older Veterans. This work will elucidate mechanisms that contribute to elevated risk for cognitive impairment in combat exposed military Veterans and can be used to inform treatments in older Veterans but also may inform preventative measures for young Veterans at risk for later life neurological disorders.

年轻成年的兵役通常伴随着各种战斗暴露 已知会增加认知障碍和阿尔茨海默氏病（AD）的风险 以后的生活（例如高血压，糖尿病，高胆固醇血症和体重指数）。 战斗暴露的重大医疗保健和社会成本已充分记录在案 这些主要的年轻成年暴露还可能促进以后的生命 直到现在才发现的条件。确定有助于的因素 老年退伍军人衰老疾病的高级风险提供了测试和 启动治疗可能会减缓这些条件进展的治疗。此外，这些数据可以 用于为年轻的，当代的退伍军人提供服务，包括 生活方式和医学变化可能会改善条件的进展，以促进以后 生活认知和行为条件。成年时代可能会发生战斗 启动“不健康衰老”的轨迹，并在生物学风险中逐渐升高 促进结构和功能性脑网络的与衰老相关的神经“断开”。 但是，迄今为止已经进行了有限的工作，将年轻的成年作战与暴露联系在一起 老年退伍军人的神经结构和功能的改变。另外，是否战斗 - 年轻成年的暴露与后期生物标志物标志的积累有关 当前未知AD，称为淀粉样蛋白，Tau，神经变性（A-T-N）框架。 那就是将年轻成年作战与晚期生活风险相关的中介机制必须 被检查。在大型TBI和应力障碍研究中心 （区域）队列研究，我们发现具有战斗暴露和症状的年轻退伍军人 另外1）具有全身生物学风险的升高； 2）显示关键大脑的改变 网络电路，例如Amygdala和默认模式网络（DMN）； 3）显示加速 结构连通性和白质微观结构的衰老趋势。我们的目标是从概念上 在拟议的工作中链接这些发现。我们建议首先通过 从成年期开始的全身健康状况升高（即'累积生物学 风险’）导致关键大脑连接损坏。累积生物学的综合作用 风险加快支持更高的结构和功能性脑网络的定义 认知功能，包括提供的内存系统和/或补偿系统 面对AD病理学的认知储备。我们将测试与战斗相关的模型 杏仁核网络失调，促进成年年轻人的系统性健康风险。这 累积生物学风险反过来有助于神经和认知决定 在年长的退伍军人中发音。这项工作将阐明有助于提升的机制 战斗暴露的退伍军人中认知障碍的风险，可用于告知 老年退伍军人的治疗方法，但也可能为年轻退伍军人的预防措施提供信息 后来的生活神经系统疾病的风险。