NAD+ Therapy for Improving Memory & Cerebrovasular Function in Patients with MCI

项目摘要/摘要 遗忘性轻度认知损害是阿尔茨海默病发展过程中最早的症状阶段 疾病(AD)，这是美国发病率和死亡率增长最快的原因之一。高架 随着年龄的增长，血压和大的弹性动脉(即大动脉和颈动脉)硬化。 并与aMCI和AD的发展有关，主要通过破坏性压力的传递 电波传导到脑血管系统，导致脑血管功能障碍和神经元损伤。风险因素 到目前为止，通过健康饮食和定期有氧运动等积极的生活方式行为来改变生活方式， 是改善急性心肌梗死患者认知功能的最有效策略。在这方面，慢性 卡路里限制(CR)预防与年龄相关的血管和认知功能障碍，部分是通过减少大弹性 动脉僵硬和血压；然而，坚持CR和其他健康的生活方式很差 在晚年、中年和老年人中。家长奖(K01 AG054731)的目标是进行 随机、安慰剂对照临床试验，研究一种新的NAD增强和CR模拟的疗效 烟酰胺核苷(NR)化合物，通过减少大弹性改善老年aMCI患者的记忆 动脉僵硬和血压升高，增加脑血流量。因为目标的年龄较大 人口，母临床试验于2020年3月暂时搁置，原因是围绕 新型冠状病毒病(新冠肺炎)，对老年人影响不成比例。最近，有证据表明 出现了将SARS CoV2感染(导致新冠肺炎的病毒)与广泛的心血管疾病联系起来 并发症包括血管内皮功能障碍、心肌炎、血栓形成和缺血性中风。 重要的是，有证据表明，即使在没有发生心血管功能障碍的人中也是如此。 新冠肺炎引发了严重的呼吸道症状。鉴于老年人罹患新冠肺炎的风险较高， SARS CoV2感染对父母试验心血管结局的潜在影响，有一个紧迫的问题 需要实施额外的保护措施，以维护母公司临床试验的安全性和完整性。 因此，本行政补充文件的目的是解决与新冠肺炎相关的对母公司的影响 通过使用增强型个人防护装备增加安全措施而获奖 (PPE)，增加工作人员以协助虚拟测试会议，维修未使用的关键研究设备 在研究暂停期间，将SARS CoV2抗体的评估添加到所有 家长试验的参与者。这些附加措施是安全恢复母公司临床试验所必需的 并保护数据的完整性，使我们能够通过以下方式继续实现NIA的重要研究目标 研究改善急性心肌梗死患者认知功能障碍的有效干预措施。

PROJECT SUMMARY/ABSTRACT Amnestic mild cognitive impairment (aMCI) is the earliest symptomatic stage in the development of Alzheimer's disease (AD), which is among the fastest growing causes of morbidity and mortality in the Unites States. Elevated blood pressure and stiffening of the large elastic arteries (i.e., the aorta and carotid arteries) occurs with aging and is linked to the development of aMCI and AD, primarily through the transmission of damaging pressure waves to the cerebral vasculature, resulting in cerebrovascular dysfunction and neuronal damage. Risk factor modification through positive lifestyle behaviors such as healthy diet and regular aerobic exercise have, thus far, been the most effective strategies for improving cognitive function in patients with aMCI. In this regard, chronic calorie restriction (CR) prevents age-related vascular and cognitive dysfunction, in part by reducing large elastic artery stiffness and blood pressure; however, adherence to CR and other healthy lifestyle behaviors is poor among late middle-aged and older adults. The objective of the parent award (K01 AG054731) is to conduct a randomized, placebo-controlled clinical trial to study the efficacy of a novel NAD-boosting and CR-mimicking compound, nicotinamide riboside (NR), for improving memory in older adults with aMCI by reducing large elastic artery stiffness and blood pressure and increasing cerebral blood flow. Because of the older age of the target population, the parent clinical trial was temporarily placed on hold in March 2020 due to concerns surrounding the novel coronavirus disease (COVID-19) which disproportionately affects older adults. More recently, evidence has emerged linking SARS CoV2 infection (the virus that causes COVID-19) to a wide range of cardiovascular complications including vascular endothelial dysfunction, myocarditis, thrombosis, and ischemic stroke. Importantly, there is evidence of cardiovascular dysfunction even among individuals who did not develop the severe respiratory symptoms attributed COVID-19. Given the higher risk of COVID-19 among older adults and the potential for SARS CoV2 infection to impact the cardiovascular outcomes of the parent trial, there is an urgent need to implement additional protective measures to preserve the safety and integrity of the parent clinical trial. Accordingly, the purpose of this administrative supplement is to address COVID-19-related impact to the parent award by incorporating additional safety measures through the use of enhanced personal protective equipment (PPE), increasing staff to assist with virtual testing sessions, servicing key research equipment that was unused during the period in which the study was on hold, and adding the assessment of SARS CoV2 antibodies to all participants in the parent trial. These additional measures are necessary safely resume the parent clinical trial and protect the integrity of the data allowing us to continue to fulfill an important research objective of NIA by investigating promising interventions for ameliorating cognitive impairment in individuals with aMCI.