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

要应对日益老龄化的退伍军人群体日益增长的医疗挑战，关键是要了解 有效的康复技术，减少与年龄相关的并存疾病，提高生活质量。到目前为止， 锻炼是为数不多的被证明可以减轻与年龄相关的大脑健康和功能衰退的干预措施之一。 在许多这些研究中，一个一致但无法解释的发现是大脑皮层激活模式的变化 在任务期间，使用血氧水平依赖(BOLD)信号和符合以下条件的fMRI进行评估 提高了任务性能。脑血管健康和功能的两个关键指标尚未得到充分研究 但可能会影响有氧运动后观察到的大胆反应的记录变化 是：1)静息或基础脑血流(灌流)到关键脑区的变化；以及2) 脑血管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，以及两者是如何 在基于任务的功能磁共振成像中，灌注和CVR有助于显示BOLD信号。与我们之前的老化情况一致 运动研究参与者将完成以下两个条件之一：1)有氧间歇训练 干预(旋转；n=44)，或2)无氧、伸展控制条件(对照；n=44)。心血管病 健身、动脉自旋标记基础脑血流灌注、CVR、基于任务的功能磁共振成像(认知-执行和 行为结果将在干预前后进行评估。具体目标将是 确定12周有氧运动干预对脑血流灌注和脑血管阻力变化的影响 年长的退伍军人。我们假设，与对照组相比，有氧训练组将有 表现为年龄相关性下降的区域的基础血流灌注和CVR增加 表现出对有氧运动(下额叶和运动皮质)的可塑性。 在过去的几十年里，研究推动了锻炼作为最重要的 对中枢神经系统健康和功能的有效干预。在这项研究的大部分前沿 使用基于任务的功能磁共振成像来量化有氧运动后皮质功能的有益变化是否大胆 锻炼身体。虽然这项研究具有变革性，但在我们定义 脑血管功能对BOLD反应有利可图的影响。我们有 我们知道，经常运动的老年人改善了血管健康，但我们不知道全部情况 运动干预对脑血管健康的影响。如果我们改善血流灌注率的假设 支持CVR，它将为当前的干预策略提供信息，并将添加重要的附加信息 关于锻炼在衰老过程中改善大脑健康的潜力。这将对衰老产生影响。 退伍军人面临脑血管功能障碍导致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.