Intermittent Hypoxia Training: A Novel Therapy for Mild Cognitive Impairment

间歇性缺氧训练：轻度认知障碍的新疗法

• 批准号: 10615133
• 负责人: Xiangrong Shi
• 金额: $ 71.4万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615133
• 关键词: Address; Adult; Air; Alzheimer' s Disease; American; Attention; Blood Pressure; Brain; Brain-Derived Neurotrophic Factor; Breathing; Cardiac; Caregivers; Cerebrovascular Circulation; Cerebrum; Chronic Obstructive Pulmonary Disease; Cognitive; Cognitive deficits; Control Groups; Coronary Arteriosclerosis; Data; Dementia; Deterioration; Development; Elderly; Emotional; Enrollment; Epidemic; Erythropoietin; Exercise Tolerance; Family; Financial Hardship; Fostering; Gases; Goals; Growth; Hemodialysis; Hippocampus; Human; Hypoxemia; Hypoxia; Impaired cognition; Individual; Intervention; Investigation; Knowledge; Measures; Memory Disorders; Memory impairment; Mission; Nerve Degeneration; Neurocognitive; Neuronal Plasticity; Nonpharmacologic Therapy; Patients; Perfusion; Periodicity; Pharmaceutical Preparations; Physiological; Placebo Control; Psyche structure; Public Health; Quality of life; Randomized; Reporting; Research; Rest; Safety; Serum; Short-Term Memory; Single-Blind Study; Societies; Therapeutic Intervention; Training; Training Programs; United States National Institutes of Health; Woman; aged; amnestic mild cognitive impairment; cerebrovascular; cognitive function; cognitive performance; disability; effective intervention; efficacious intervention; evidence base; follow up assessment; human old age (65+); hypertensive; improved; innovation; intravenous injection; men; mild cognitive impairment; neurogenesis; neuroprotection; novel; novel therapeutics; older patient; phase I trial; pre-clinical; prevent; preventive intervention; progression risk; recombinant human erythropoietin; therapeutically effective; tissue oxygenation; young adult

Currently, there is no intervention capable of curing or even slowing the cognitive impairment and neurodegeneration associated with Alzheimer’s disease (AD). Our long-term goal is to develop safe and effective, preventive and therapeutic interventions to slow, halt, and/or reverse cognitive decline and neurodegenerative progression to AD-dementias. The objective of this application is to confirm the safety and establish the efficacy of an 8-week intermittent-hypoxia training (IHT) program, which can be applied as a novel treatment to improve neurocognitive function in patients with amnestic mild cognitive impairment (aMCI), a pre-clinical state associated with a heightened risk of progressing to AD. The central hypothesis is that IHT imparted by brief, cyclic, repetitive, low-intensity, normobaric hypoxia exposures is a safe and effective means of optimizing cerebral circulation and conferring neuroprotection, thereby improving cognitive function in patients with aMCI. IHT has been found to promote neuroprotection, neuroplasticity, and neurogenesis, and to improve cerebrovascular function and cerebral tissue oxygenation. Therefore, the rationale for this proposed research is that, by mobilizing neuroprotective growth/trophic factors and by improving cerebral circulation, IHT is expected to be a powerful intervention to prevent and/or reverse cognitive decline and neurodegenerative progression to AD-dementias. The specific aims are proposed to confirm the safety and efficacy of an 8-week IHT program for improving neurocognitive function in patients with aMCI, and to demonstrate IHT’s capacity to improve cerebrovascular function at rest and during mental, physiological and hypoxia challenges, and mobilize neuroprotective growth/trophic factors. This proposed phase I trial is innovative and its contribution is significant because it will be the first step in a continuum of research that is expected to develop a specific and practical intervention which can be safely and effectively applied to elderly patients to prevent and treat cognitive impairment and neurodegeneration. Ultimately, this investigation is expected to foster the development of novel interventions for prevention and treatment of mild cognitive impairment and AD-dementias.

目前，没有任何干预措施能够治愈甚至减缓认知障碍和 与阿尔茨海默病（AD）相关的神经退行性疾病。我们的长期目标是发展安全、 有效的预防性和治疗性干预措施，以减缓、停止和/或逆转认知能力下降 神经退行性进展为 AD 痴呆。此应用程序的目的是确认安全性 并建立为期 8 周的间歇性缺氧训练 (IHT) 计划的功效，该计划可作为 一种改善遗忘性轻度认知障碍患者神经认知功能的新疗法 (aMCI)，一种与进展为 AD 风险增加相关的临床前状态。中心假设是 通过短暂、循环、重复、低强度、常压缺氧暴露进行的 IHT 是一种安全且可靠的方法。 优化脑循环、赋予神经保护作用的有效手段，从而改善 aMCI 患者的认知功能。 IHT 被发现可以促进神经保护、神经可塑性、 和神经发生，并改善脑血管功能和脑组织氧合。因此， 这项拟议研究的基本原理是，通过调动神经保护性生长/营养因子并通过 改善脑循环，IHT 有望成为预防和/或逆转的有力干预措施 认知能力下降和神经退行性进展为 AD 痴呆。提出的具体目标是 确认为期 8 周的 IHT 计划改善患者神经认知功能的安全性和有效性 与 aMCI 合作，并证明 IHT 改善静息时和运动期间脑血管功能的能力 精神、生理和缺氧挑战，并动员神经保护性生长/营养因子。这 拟议的第一阶段试验具有创新性，其贡献是重大的，因为它将是 预计将开发出可安全实施的具体且实用的干预措施的连续研究 并有效应用于老年患者预防和治疗认知障碍和神经退行性疾病。 最终，这项调查预计将促进预防和预防新型干预措施的发展。 治疗轻度认知障碍和 AD 痴呆。