Intermittent Hypoxia Training: A Novel Therapy for Mild Cognitive Impairment

目前，没有能够治愈甚至减缓认知障碍的干预措施， 与阿尔茨海默病（AD）相关的神经变性。我们的长期目标是发展安全、 有效的预防和治疗干预措施，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。本申请的目的是确认 并确定为期8周的抗缺氧训练（IHT）计划的有效性，该计划可作为 一种改善遗忘型轻度认知障碍患者神经认知功能的新疗法 aMCI是一种与进展为AD的风险升高相关的临床前状态。核心假设是 短暂的、周期性的、重复的、低强度的常压缺氧暴露所引起的IHT是一种安全的， 优化脑循环和赋予神经保护的有效手段，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 这项研究的基本原理是，通过动员神经保护性生长/营养因子， 改善脑循环，IHT有望成为预防和/或逆转 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 证实了8周IHT计划改善患者神经认知功能的安全性和有效性 与aMCI，并证明IHT的能力，以改善脑血管功能，在休息和 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是创新的，其贡献是重大的，因为它将是一个 一个连续的研究，预计将开发一个具体的和实际的干预，可以安全地 有效地应用于老年患者预防和治疗认知障碍和神经退行性变。 最终，这项研究有望促进新的预防干预措施的发展， 治疗轻度认知障碍和AD痴呆。

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.