Asymptomatic Carotid Stenosis and Mobility Function with Exercise Intervention (ACCOF-Ex)

无症状性颈动脉狭窄(ACAS)影响约10%的老年人。卒中的临床转归 已经得到了广泛的研究。最近的文献，包括我们的初步数据，表明适度(50- 69%)和严重(≥70%)ACAS也与跌倒、平衡和活动功能障碍有关。初级阶段 这些缺陷背后的假设因素是大脑灌流不足。在重度ACAS患者中，颈动脉 血管重建术已被证明可以改善血流灌注，以及平衡和活动障碍。病人 中度狭窄患者在ACAS患者中所占比例要大得多，不符合手术条件。使用 据估计，有830,000名退伍军人患有中度ACAS，正在制定有针对性的治疗策略，以改善BALL- 步行和活动功能是预防残疾和保持功能独立性的关键。 有针对性的有氧和平衡运动增加脑血流，改善平衡和活动功能 无颈动脉狭窄的老年人行冠状动脉介入治疗。基于这些发现，我们假设有氧运动和运动- 延长平衡(AeroBal)运动干预将改善患有MOD的退伍军人的平衡和活动功能 在增强脑血流灌注的同时增强ACAS。对于这项CDA-2，我建议进行一项随机研究，以评估 12周有指导的AeroBal运动计划对老年高血压患者平衡和活动功能的影响 中度ACAS与标准护理对照。为此，我提出以下目标： 目的1.确定为期12周的有监督的空中平衡训练计划对平衡和活动能力的影响 中度ACAS退伍军人的功能。假设：有监督的AeroBal演习加上标准护理 将导致平衡和机动性的更大改善(主要结果：迷你平衡评估系统 试验[Mini Best est])与单纯标准护理降低血管危险因素的比较 阿卡斯。次要结果测量将包括预期跌倒的比率和身体功能的测量。 目的2.确定为期12周的监督AeroBal运动计划对脑血流灌注的影响 中度ACAS的存在。假设：有监督的AeroBal演习加上标准护理将导致 脑血流灌注的更大改善(主要测量：灌注加权磁共振成像 和二次测量：经颅多普勒)与单独降低血管风险因素的标准护理相比 在中度颈动脉狭窄患者中。我们还将探索功能性近红外光谱学作为一种新颖的 血流灌注测量，非常适合临床翻译，因为它评估移动任务期间的血流灌注。 探索性分析将考察平衡和活动功能变化之间的关系，以及 脑部血流灌注的变化。假设：运动导致的平衡和活动功能的改变将是 与脑灌注的变化有关，与已知血管危险因素的变化无关。 认为运动是一种改善脑血流灌注、平衡和活动功能的干预措施 中度ACAS患者的TION可导致临床管理、功能和功能的显著变化 这些不适合手术的患者的独立性和生活质量。我的长期目标 成为一名独立的退伍军人管理局调查员，进行有针对性的干预，以保护和改善功能指数。 急性冠脉综合征患者的悬垂性。更具体地说，我的目标是阐明脑灌注在 VA患者亚群中平衡和活动功能障碍的发展。因此，作为一名退伍军人管理局的外科医生-- 我的目标不仅是改善我的患者的临床结果，而且要改善更广泛的血管患者群体的临床结果。 通过运动干预。有了建议的退伍军人事务部CDA-2奖项，我将能够获得额外的教育和 指导平衡和活动功能评估、运动干预、临床试验设计和 统计分析，先进的脑血管成像，以及研究的领导和管理 一队。从这次机会中获得的技能和经验将使我为独立的职业生涯做好准备 退伍军人事务部的调查员。

Asymptomatic carotid artery stenosis (ACAS) affects ~10% of older adults. The clinical outcome of stroke has been studied extensively. Recent literature, including our preliminary data, demonstrates that moderate (50- 69%) and severe (≥70%) ACAS are also associated with falls and balance and mobility dysfunction. The primary hypothesized factor underlying these deficits is cerebral hypoperfusion. In patients with severe ACAS, carotid revascularization has been shown to improve perfusion, as well as balance and mobility dysfunction. Patients with moderate stenosis, who form a much larger proportion of ACAS patients, do not qualify for surgery. With 830,000 Veterans estimated to have moderate ACAS, developing targeted treatment strategies to improve bal- ance and mobility function is critical to prevent disability and preserve functional independence. Targeted aerobic and balance exercises increase cerebral perfusion and improve balance and mobility func- tion in older adults without carotid stenosis. Based on these findings, we hypothesize that an aerobic and chal- lenging balance (AeroBal) exercise intervention will improve balance and mobility function in Veterans with mod- erate ACAS while enhancing cerebral perfusion. For this CDA-2, I propose a randomized study to evaluate the effects of a 12-week supervised AeroBal exercise program on balance and mobility function in patients with moderate ACAS versus standard-of-care controls. Towards this goal, I propose the following Aims: Aim 1. Determine the effect of a 12-week supervised AeroBal exercise program on balance and mobility function in Veterans with moderate ACAS. Hypothesis: Supervised AeroBal exercises plus standard-of-care will lead to greater improvement in balance and mobility (primary outcome: Mini Balance Evaluation Systems Test [Mini BESTest]) compared to standard-of-care vascular risk-factor reduction alone in patients with moderate ACAS. Secondary outcome measures will include rate of prospective falls and measures of physical function. Aim 2. Determine the effect of a 12-week supervised AeroBal exercise program on cerebral perfusion in the presence of moderate ACAS. Hypothesis: Supervised AeroBal exercises plus standard-of-care will lead to greater improvement in cerebral perfusion (primary measure: perfusion-weighted magnetic resonance imaging and secondary measure: transcranial Doppler) compared to standard-of-care vascular risk-factor reduction alone in patients with moderate carotid stenosis. We will also explore functional near-infrared spectroscopy as a novel measure of perfusion that is ideal for clinical translation as it assesses perfusion during mobility tasks. An exploratory analysis will examine the relationship between changes in balance and mobility function and changes in cerebral perfusion. Hypothesis: Exercise-induced changes in balance and mobility function will be related to changes in cerebral perfusion independent of changes in known vascular risk factors. The identification of exercise as an intervention to improve cerebral perfusion and balance and mobility func- tion in patients with moderate ACAS could lead to significant changes in the clinical management, functional independence, and quality of life of this patient population who are not candidates for surgery. My long-term goal is to become an independent VA investigator in targeted interventions to preserve and improve functional inde- pendence in ACAS patients. More specifically, I aim to elucidate the role that cerebral perfusion plays in the development of balance and mobility dysfunction in this VA patient subset. Thus, by being a VA surgeon-scien- tist, I aim to improve the clinical outcomes of not only my patients, but the broader vascular patient population via exercise interventions. With the proposed VA CDA-2 award, I will be able to acquire additional education and mentorship in balance and mobility function assessments, exercise intervention, clinical trial design and statistical analysis, advanced cerebrovascular imaging, and leadership and management of a study team. The skills and experience derived from this opportunity will prepare me for a career as an independent investigator within the VA RR&D.