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

项目摘要 候选人：克里斯托弗·R。Martens博士，是一个在老化综合生理学方面接受培训的研究员， 科罗拉多博尔德大学。在这个K01应用程序中，Martens博士的目标是研究一种新型NAD+的疗效。 用于减少大弹性动脉的促进和模拟热量限制的化合物，烟酰胺核苷（NR） 遗忘型轻度认知功能障碍（aMCI）老年人的僵硬度和血压， 改善脑血管、认知和神经功能的结果。他的近期目标是获得 过渡到独立调查员所需的研究培训和专业技能。他的长- 一个长期的目标是建立自己的研究计划，重点是确定改善战略， 脑血管和认知/神经功能，并降低老年人患阿尔茨海默病（AD）的风险。 职业发展规划：Martens博士建议通过以下方式促进其职业发展：1）获得 脑血管、认知和神经功能评估的新技能，以支持他提出的 研究计划; 2）接受aMCI和AD病理生理学，老年医学和生物统计学方面的培训; 3）完善 他的专业技能，通过正式的课程工作，出席和介绍每周杂志俱乐部， 大学研讨会和国家科学会议，并通过与他的指导团队的定期互动。 环境：马滕斯博士将在一个优秀的老龄化研究环境中接受培训， 专业导师团队将为他提供研究和职业发展培训。主 导师Seals博士是一位国际公认的NIA资助的科学家，拥有成功的 指导血管老化研究。共同导师休森博士是脑血管功能的领先专家 Bettcher博士在评估aMCI患者的认知功能方面拥有丰富的经验。 博士Banich是CU-Boulder神经成像中心的主任，在神经成像方面有丰富的经验。 提出了基于MRI的神经元功能和结构评估。麦奎因博士是生物统计学主任 在CU-Boulder临床和转化研究中心（CTRC），并定期提供指导和 为进行临床试验的学员和教员提供咨询。共同导师波特博士和施瓦茨博士是资深的 NIA研究人员分别具有AD和老年医学方面的专业知识，他们的指导将 补充研究培训和目标。研究：aMCI是最早的症状阶段， AD是美国发病率和死亡率增长最快的原因之一。加强 大的弹性动脉（即，主动脉和颈动脉）随着年龄的增长而发生， aMCI和AD的发展，主要是通过将破坏性压力波传输到大脑 血管，导致脑血管功能障碍和神经元损伤。拟议的研究旨在 测试一种新型的模拟CR的膳食补充剂NR在降低患有以下疾病的患者的动脉硬度方面的功效： aMCI，并将这些变化与改善的脑血管、认知和神经元功能相关联。

PROJECT SUMMARY CANDIDATE: Christopher R. Martens, Ph.D., is a fellow training in the integrative physiology of aging at the University of Colorado Boulder. In this K01 application, Dr. Martens aims to study the efficacy of a novel NAD+ boosting and calorie restriction-mimetic compound, nicotinamide riboside (NR), for reducing large elastic artery stiffness and blood pressure in older adults with amnestic mild cognitive impairment (aMCI) and to relate these outcomes to improvements in cerebrovascular, cognitive and neuronal function. His immediate goal is to acquire the research training and professional skills necessary to transition to an independent investigator. His long- term goal is to establish his own research program, with a focus on identifying strategies for improving cerebrovascular and cognitive/neuronal function and reducing risk of Alzheimer's disease (AD) in older adults. CAREER DEVELOPMENT PLAN: Dr. Martens proposes to enhance his career development by: 1) acquiring new skills in the assessment of cerebrovascular, cognitive and neuronal function to support his proposed research plan; 2) receiving training in aMCI and AD pathophysiology, geriatrics and biostatistics; and 3) refining his professional skills through formal course work, attendance and presentations at weekly journal clubs, university seminars, and national scientific meetings, and through regular interactions with his mentoring team. ENVIRONMENT: Dr. Martens will train in an outstanding aging research environment supported by a multi- disciplinary team of mentors who will provide him with research and career development training. The primary mentor, Dr. Seals, is an internationally recognized NIA-funded scientist with a strong record of successful mentoring in vascular aging research. Co-Mentor Dr. Hughson is a leading expert in cerebrovascular function and brain aging, and Dr. Bettcher has extensive experience assessing cognitive function in patients with aMCI. Dr. Banich is director of the neuroimaging center at CU-Boulder and has extensive experience with the proposed MRI-based assessments of neuronal function and structure. Dr. McQueen is director of biostatistics at the CU-Boulder Clinical and Translational Research Center (CTRC) and regularly provides mentoring and consulting to trainees and faculty conducting clinical trials. Co-mentors Dr. Potter and Dr. Schwartz are senior NIA investigators with expertise in AD and geriatric medicine, respectively, and their mentorship will complement the research training & objectives. RESEARCH: aMCI is the earliest symptomatic stage in the development of AD, which is among the fastest growing causes of morbidity and mortality in the US. Stiffening of the large elastic arteries (i.e., the aorta and carotid arteries) occurs with aging and has been 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. The proposed research seeks to test the efficacy a novel CR-mimicking dietary supplement, NR, for lowering arterial stiffness in patients with aMCI and associating these changes with improved cerebrovascular, cognitive and neuronal function.