The POINTER Neurovascular Ancillary Study

项目摘要 脑缺血相关的脑血流调节功能障碍在脑缺血的病理生理学中起着重要的作用。 大脑老化并可能使老化的大脑更容易受到共病状况的破坏性影响， 如高血压、糖尿病和高胆固醇血症。两个关键的调节机制的缺陷 局部和全身水平的脑血流（即，脑自动调节和压力反射敏感性， 在日常生活的正常活动过程中， 为反复缺血性损伤、进行性认知下降和阿尔茨海默病奠定基础， 相关性痴呆（ADRD）因此，测量大脑自动调节和压力反射敏感性可以提供 ADRD研究中神经变性的早期生物标志物，特别是那些专注于预防的研究。美国 通过生活方式干预降低风险来保护大脑健康的研究（美国POINTER）正在进行中， 一项多中心随机临床试验，旨在研究是否随机分为两种生活方式之一 形式和强度不同的干预措施在2年内改变了2，000名老年人的认知轨迹 60-79岁，认知正常，但由于一级家族史，痴呆风险增加 严重的记忆障碍、久坐不动的生活方式、不良的饮食和次优的心脏代谢健康。的 拟议的辅助研究POINTER-NV将全面评估自主神经功能、大脑 通过评价主动脉、颈动脉和脑血流动力学， 使用互补技术（即，超声、眼压测量、连续血压和心率 监测）在各种条件下（即，在休息时，在立位压力期间，以及在二氧化碳 吸入）。这些神经血管结局将在基线、第1年和第2年在500 POINTER中进行评估 5个临床研究中心的参与者（每个研究中心约100人;每个干预组250人）。主要目的是评估 POINTER生活方式干预对大脑自动调节和压力反射敏感性的影响;我们还将 评估干预对主动脉僵硬度、颈动脉僵硬度和脑血管反应性的影响。此外，本发明还提供了一种方法， POINTER-NV将检查这些神经血管结局是否与认知相关（评估 每6个月评估一次，作为母体试验的一部分）和大脑结构和功能（每1-2年评估一次，作为母体试验的一部分）。 a脑成像辅助研究）。通过利用U.S. POINTER的丰富资源和基础设施， 创新和具有成本效益的辅助研究提供了一个前所未有的和时间有限的机会， 母试验的范围和影响，并解决该领域的关键研究重点。

PROJECT SUMMARY Age-related dysfunction of cerebral blood flow regulation plays an important role in the pathophysiology of brain aging and likely renders the aging brain more susceptible to the damaging effects of comorbid conditions, such as hypertension, diabetes, and hypercholesterolemia. Impairments in two key mechanisms that regulate cerebral blood flow at the local and systemic level (i.e., cerebral autoregulation and baroreflex sensitivity, respectively) may promote cerebral hypoperfusion in the course of normal activities of daily living, thereby setting the stage for repeated ischemic insults, progressive cognitive decline, and Alzheimer's disease and related dementias (ADRD). Thus, measuring cerebral autoregulation and baroreflex sensitivity may provide early biomarkers of neurodegeneration in ADRD studies, particularly those focused on prevention. The U.S. study to PrOtect brain health through lifestyle INTErvention to Reduce risk (U.S. POINTER) is an ongoing multi-center randomized clinical trial designed to investigate whether randomization to one of two lifestyle interventions that differ in format and intensity alters cognitive trajectory over 2 years in 2,000 older adults aged 60-79 years who are cognitively normal but at increased risk for dementia due to first degree family history of significant memory impairment, sedentary lifestyle, poor diet, and suboptimum cardiometabolic health. The proposed ancillary study POINTER-NV will comprehensively assess autonomic function, cerebral autoregulation, and vascular structure and function by evaluating aortic, carotid, and cerebral hemodynamics using complementary techniques (i.e., ultrasound, tonometry, and continuous blood pressure and heart rate monitoring) under a variety of conditions (i.e., at rest, during orthostatic stress, and during carbon dioxide inhalation). These neurovascular outcomes will be assessed at baseline, Year 1, and Year 2 in 500 POINTER participants across 5 clinical sites (~100 per site; 250 per intervention arm). The primary aim is to assess the effects of the POINTER lifestyle intervention on cerebral autoregulation and baroreflex sensitivity; we will also assess intervention effects on aortic stiffness, carotid stiffness, and cerebral vasomotor reactivity. In addition, POINTER-NV will examine whether these neurovascular outcomes are associated with cognition (assessed every 6 months as part of the parent trial) and brain structure and function (assessed every 1-2 years as part of a Brain Imaging ancillary study). By leveraging the rich resources and infrastructure of U.S. POINTER, this innovative and cost-effective ancillary study presents an unprecedented and time-limited opportunity to expand the scope and impact of the parent trial and address key research priorities in the field.