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

NAD 改善记忆疗法

• 批准号: 10117160
• 负责人: Christopher Martens
• 金额: $ 13.31万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117160
• 关键词: Accounting; Acute; Adherence; Adult; Aerobic Exercise; Affect; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease risk; Amyloid beta-Protein; Antioxidants; Aorta; Area; Arteries; Attention; Behavior; Biometry; Blood; Blood Flow Velocity; Blood Pressure; Blood Vessels; Blood flow; Brain; Buffers; Caloric Restriction; Cardiovascular Diseases; Carotid Arteries; Center for Translational Science Activities; Cerebrovascular Disorders; Cerebrovascular system; Chronic; Clinical Research; Cognitive; Colorado; Complement; Conduct Clinical Trials; Consult; Control Groups; Controlled Clinical Trials; Deacetylase; Dementia; Development; Development Plans; Disease; Doctor of Philosophy; Double-Blind Method; Elderly; Environment; Enzymes; Episodic memory; Faculty; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Geriatrics; Goals; Gold; Heart; Human; Hypercapnia; Impaired cognition; Impairment; Individual; Infusion procedures; Internal carotid artery structure; International; Intervention; Journals; Language; Life Style; Link; Magnetic Resonance Imaging; Martens; Measures; Mediating; Memory; Memory Loss; Mentors; Mentorship; Microcirculation; Modification; Morbidity - disease rate; Mus; Nerve Degeneration; Neurons; Oral; Outcome; Oxidative Stress; Pathologic; Pathology; Patients; Perfusion; Pharmacology; Physiologic pulse; Physiology; Placebos; Postdoctoral Fellow; Public Health; Randomized; Research; Research Personnel; Research Training; Rest; Risk; Risk Factors; SIRT1 gene; Safety; Saline; Scientist; Short-Term Memory; Sirtuins; Structure; Supplementation; Systole; Testing; Therapeutic; Training; Translating; Universities; Vascular Cognitive Impairment; Work; abeta deposition; age related; aging brain; amnestic mild cognitive impairment; arterial stiffness; base; career development; cerebrovascular; cognitive function; cost effective; dietary supplements; efficacy study; efficacy testing; episodic memory impairment; executive function; experience; good diet; healthy lifestyle; improved; indexing; insight; interest; meetings; middle age; middle cerebral artery; mimetics; modifiable risk; mortality; mouse model; multidisciplinary; neuroimaging; neurovascular coupling; nicotinamide riboside supplementation; nicotinamide-beta-riboside; novel; oral supplementation; pressure; prevent; processing speed; programs; relating to nervous system; research and development; response; seal; skills; standard measure; transmission process; vertebral artery

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.

项目概要 候选人：克里斯托弗·R·马滕斯 (Christopher R. Martens) 博士，是一位在衰老综合生理学方面接受培训的研究员 科罗拉多大学博尔德分校。在此 K01 应用中，Dr. Martens 旨在研究新型 NAD+ 的功效 增强和热量限制模拟化合物，烟酰胺核苷 (NR)，用于减少大弹性动脉 患有遗忘型轻度认知障碍 (aMCI) 的老年人的僵硬和血压，并将这些联系起来 改善脑血管、认知和神经功能的结果。他的近期目标是获得 过渡为独立研究者所需的研究培训和专业技能。他的长 学期目标是建立自己的研究计划，重点是确定改进的策略 脑血管和认知/神经元功能，并降低老年人患阿尔茨海默病 (AD) 的风险。 职业发展计划：Dr. Martens 建议通过以下方式增强职业发展： 1) 获得 评估脑血管、认知和神经元功能的新技能支持他的提议 研究计划； 2) 接受aMCI和AD病理生理学、老年病学和生物统计学方面的培训； 3) 精炼 他通过正式课程、每周期刊俱乐部的出席和演讲获得的专业技能， 大学研讨会和国家科学会议，以及通过与他的指导团队的定期互动。 环境：Dr. Martens 将在由多方支持的杰出老化研究环境中接受培训 学科导师团队将为他提供研究和职业发展培训。初级 导师 Seals 博士是一位国际公认的 NIA 资助的科学家，拥有良好的成功记录 血管老化研究的指导。共同导师 Hughson 博士是脑血管功能方面的领先专家 Bettcher 博士在评估 aMCI 患者的认知功能方面拥有丰富的经验。 Banich 博士是 CU-Boulder 神经影像中心主任，在以下领域拥有丰富的经验： 提出基于 MRI 的神经元功能和结构评估。麦奎因博士是生物统计主任 在 CU-Boulder 临床和转化研究中心 (CTRC) 工作，并定期提供指导和 为进行临床试验的学员和教师提供咨询。共同导师波特博士和施瓦茨博士是资深人士 NIA 研究人员分别在 AD 和老年医学方面拥有专业知识，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。硬化 大弹性动脉（即主动脉和颈动脉）的退化会随着年龄的增长而发生，并且与 aMCI 和 AD 的发展，主要是通过将破坏性压力波传输至大脑 血管系统，导致脑血管功能障碍和神经元损伤。拟议的研究旨在 测试新型 CR 模拟膳食补充剂 NR 降低动脉僵硬度的功效 aMCI 并将这些变化与脑血管、认知和神经功能的改善联系起来。