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，没有干预措施能够治愈甚至减缓认知障碍，并且 与阿尔茨海默氏病（AD）相关的神经变性。我们的长期目标是发展安全和 有效，预防和治疗性干预措施减慢，停止和/或反向认知能力下降，并且 神经退行性的进展到Ad-Denemias。该应用的目的是确认安全 并建立为期8周的间歇性避氧化训练（IHT）计划的效率，可以应用于 一种新的治疗方法，可改善最轻度认知障碍患者的神经认知功能 （AMCI），一种临床前状态，与升级为AD的风险更高相关。中心假设是 IHT通过简短的，循环，重复，低强度，正常的缺氧暴露是一种安全， 优化脑循环和会议神经保护的有效方法，从而改善 AMCI患者的认知功能。已经发现IHT促进神经保护，神经塑性， 和神经发生，并改善脑血管功能和脑组织氧合。因此， 这项拟议的研究的理由是，通过动员神经保护性生长/营养因素以及通过 改善脑循环，IHT有望是预防和/或反向的强大干预措施 认知能力下降和神经退行性的进展。提出了具体目的 确认为期8周的IHT计划的安全性和效率，以改善患者的神经认知功能 使用AMCI，并展示IHT在休息和期间提高脑血管功能的能力 精神，身体和低氧挑战，动员神经保护性生长/营养因素。这 拟议的第一阶段试验具有创新性，其贡献很重要，因为它将是 期望开发特定且实用的干预措施的研究连续性可以安全地进行 并有效地应用于老年患者，以预防和治疗认知障碍和神经退行性。 最终，这项投资有望促进预防新干预措施的发展 治疗轻度认知障碍和AD-诱导。