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

青年时期的服兵役通常伴随着各种战斗经历。 已知会增加认知障碍和阿尔茨海默病(AD)的风险 晚年生活(如高血压、糖尿病、高胆固醇血症和体重指数)。虽然 战斗暴露的重大医疗保健和社会成本是有充分记录的，它是 可能这些初级的青春期接触额外促进了晚年的次要生活 直到现在才被发现的情况。确定促成因素 老年退伍军人患老年病的高级风险提供了测试和 开始治疗，可能会减缓这些疾病的进展。此外，这些数据可能 用于为照顾年轻的当代退伍军人提供信息，包括启动 生活方式和医学改变可能会改善后来促进的疾病的进展 生活认知和行为状况。青年时期的战斗暴露是有可能的 开启了一条“不健康老龄化”的轨道，生物风险逐渐上升， 促进结构和功能大脑网络与衰老相关的神经“断开”。 然而，迄今为止开展的工作有限，将青少年接触战斗与 老年退伍军人神经结构和功能的改变。此外，无论是战斗- 青年时期的暴露与老年人晚年生物标记物特征的积累有关 AD被称为淀粉样蛋白，tau，神经退行性变(A-T-N)框架，目前尚不清楚。 因此，将青年时期的战斗暴露与晚年生活风险联系起来的中介机制必须 接受检查。在大型脑创伤和应激障碍翻译研究中心 (TRADS)队列研究，我们发现有战斗暴露和症状的年轻退伍军人 此外，1)系统性生物风险升高；2)显示临界脑的变化 网络电路，如杏仁核和默认模式网络(DMN)；以及3)显示加速 结构连通性和白质微观结构的老化趋势。我们的目标是在概念上 将这些发现与拟议的工作联系起来。我们建议，晚年风险首先通过 从青壮年开始的全身健康状况的提升(即 风险)，这会导致关键的大脑连接受损。累积生物效应的综合效应 风险加速支持更高的结构和功能的大脑网络的恶化 认知功能，包括记忆系统和/或补偿系统，提供 面对AD病理的认知储备。我们将测试一个与战斗相关的模型 杏仁核网络失调促进青壮年全身性健康风险。这 累积的生物风险反过来又会导致神经和认知的恶化，即 在年长的退伍军人中发音。这项工作将阐明导致升高的机制 暴露在战斗中的退伍军人认知损害的风险，可以用来告知 老年退伍军人的治疗，但也可能为年轻退伍军人的预防措施提供信息， 有患上晚年神经性疾病的风险。

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.