The POINTER Neurovascular Ancillary Study

项目总结 增龄性脑血流调节功能障碍在老年高血压病的病理生理机制中起重要作用 大脑老化，很可能使老化的大脑更容易受到并存条件的损害， 如高血压、糖尿病和高胆固醇血症。监管的两个关键机制的损害 局部和全身水平的脑血流量(即大脑自动调节和压力反射敏感性， 可促进日常生活活动过程中的脑低灌流，从而 为反复的缺血性侮辱、进行性认知能力下降和阿尔茨海默病以及 相关痴呆(ADRD)。因此，测量大脑自动调节和压力感受器反射敏感性可以提供 ADRD研究中神经变性的早期生物标记物，特别是那些侧重于预防的研究。美国 通过生活方式干预以降低风险来保护大脑健康的研究正在进行中(美国指针) 旨在调查随机选择两种生活方式之一的多中心随机临床试验 不同形式和强度的干预在2年内改变了2000名老年人的认知轨迹 60-79岁，认知正常，但因一级家族史而患痴呆症风险增加 严重的记忆障碍，久坐的生活方式，糟糕的饮食，以及次佳的心脏代谢健康。这个 拟议的辅助研究POINTER-NV将全面评估自主神经功能、大脑 通过评估主动脉、颈动脉和脑血流动力学，自动调节和血管结构和功能 使用补充技术(即超声、眼压测量和持续血压和心率 监测)在各种条件下(即，休息、立位应激期间和二氧化碳期间 吸入)。这些神经血管结果将在基线、第一年和第二年在500指针中进行评估 参与者来自5个临床站点(每个站点约100个；每个干预组250个)。主要目标是评估 指针式生活方式干预对脑自我调节和压力感受器敏感性的影响 评估干预对主动脉僵硬、颈动脉僵硬和脑血管舒缩反应性的影响。此外, POINTER-NV将检查这些神经血管结果是否与认知相关(经评估 作为父母试验的一部分，每6个月)和大脑结构和功能(作为 脑成像辅助研究)。通过利用美国指针公司丰富的资源和基础设施，这 创新和经济高效的辅助研究提供了一个前所未有的、有时间限制的扩展机会 家长试验的范围和影响，并解决该领域的关键研究优先事项。

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.