Graded Intensity Aerobic Exercise to Improve Cerebrovascular Function and Performance in Aged Veterans

为了解决日益增长的老龄化退伍军人人口的医疗保健挑战，关键是要了解 有效的康复技术，减轻与年龄有关的并发症，提高生活质量。到目前为止， 锻炼是少数几种经证实的干预措施之一，可以减轻与年龄有关的大脑健康和功能下降。 在许多这些研究中，一个一致但无法解释的发现是皮层激活模式的变化 在任务期间，使用血氧水平依赖（BOLD）信号与fMRI进行评估， 提高任务绩效。脑血管健康和功能的两个关键指标尚未得到充分研究 但可能影响在有氧活动后观察到的BOLD反应的记录变化 是：1）关键脑区的静息或基础脑血流（灌注）的变化; 2） 脑血管系统在需求增加时扩张的能力，称为脑血管反应性 （CVR）。我们的目标是量化有氧运动对脑血管功能的影响， 灌注和CVR有助于BOLD信号在基于任务的功能磁共振成像。与我们之前的老化情况一致 和运动研究参与者将完成两个条件之一：1）有氧，间歇训练 干预（Spin; n = 44），或2）非有氧拉伸对照条件（对照; n = 44）。心血管 健康，基础脑灌注的动脉自旋标记，CVR，基于任务的功能磁共振成像（认知-执行和 运动）和行为结果将在干预前后进行评估。具体目标将 确定12周有氧运动干预对脑灌注和CVR变化的影响， 老退伍军人我们假设，与对照组相比，有氧训练组 在表现出年龄相关性下降的区域中基础灌注和CVR增加， 被证明对有氧运动具有可塑性（下额叶和运动皮质）。 过去几十年的研究推动了运动的持续推广， 对中枢神经系统健康和功能的有效干预。在这项研究的最前沿， 是使用基于任务的功能磁共振成像BOLD来量化有氧运动后皮质功能的有益变化， 锻炼的虽然具有变革性，但这项研究的真正影响范围有限，直到我们能够定义 脑血管功能对BOLD反应的有益变化的影响。我们 我们知道，身体活动的老年人改善了血管健康，但我们不知道其全部原因。 运动干预对脑血管健康影响。如果我们关于改善灌注和 CVR得到支持，它将为当前的干预策略提供信息，并将增加重要的额外信息 关于运动对改善老年人大脑健康的潜力。这将对衰老产生影响 退伍军人有患脑血管功能障碍引起的神经退行性疾病的风险。

To address the growing healthcare challenges of an aging Veteran population it is critical to understand effective rehabilitation techniques that mitigate age-related co-morbidity and improve quality of life. To date, exercise is one of a few proven interventions that attenuates age-related declines in brain health and function. A consistent but unexplained finding in many of these studies is a change in the cortical activation pattern during task, assessed using blood-oxygen-level dependent (BOLD) signal with fMRI that corresponds with improved task performance. Two key metrics of cerebrovascular health and functioning that are underexplored but may influence the documented changes in the BOLD response that is observed with post-aerobic activity are: 1) changes in resting or basal cerebral blood flow (perfusion) to key brain regions; and 2) changes in the ability of cerebrovasculature to dilate in the face of increased demand, termed cerebrovascular reactivity (CVR). Our goal is to quantify the impact of aerobic exercise on cerebrovascular function and how both perfusion and CVR contributes to the BOLD signal during task-based fMRI. Consistent with our previous aging and exercise studies participants will complete one of two conditions; 1) an aerobic, interval-training intervention (Spin; n= 44), or 2) a non-aerobic, stretching control condition (Control; n=44). Cardiovascular fitness, arterial spin labeling for basal cerebral perfusion, CVR, task-based fMRI (cognitive-executive and motor), and behavioral outcomes will be assessed before and after the interventions. The specific aims will determine the effect of a 12-week aerobic exercise intervention on changes in cerebral perfusion and CVR in older Veterans. We hypothesize that compared to the Control group, the aerobically-trained group will have increased basal perfusion and CVR in areas that demonstrate age-related decline and that have been demonstrated to be malleable to aerobic exercise (inferior frontal and motor cortices). Research over the last few decades have driven the continual promotion of exercise as one of the most impactful interventions of central nervous system health and function. At the forefront of much of this research is the use of task-based fMRI BOLD to quantify beneficial changes in cortical function following aerobic exercise. While transformative, the true impact of this research is limited in scope until we can define the influence of cerebrovascular function on the well-documented beneficial change in BOLD response. We do know that older adults who are physically active have improved vascular health but we do not know the full impact of an exercise intervention on cerebrovascular health. If our hypotheses of improved perfusion and CVR is supported it would inform current intervention strategies and would add important additional information about the potential of exercise to improve brain health in aging. This would have implications for aging Veterans at risk for neurodegenerative disease brought on by cerebrovascular dysfunction.