Intermittent Hypoxia Training: A Novel Therapy for Mild Cognitive Impairment

目前，还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)相关的神经退行性变。我们的长期目标是发展安全和 有效的预防和治疗干预措施，以减缓、阻止和/或扭转认知能力下降和 神经退行性进展为阿尔茨海默病。此应用程序的目的是确认安全 并建立为期8周的间歇低氧训练(IHT)计划的有效性，该计划可应用于 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的高风险相关的临床前状态。中心假设是 通过短暂、周期性、重复、低强度、常压低氧暴露所传授的IHT是一种安全和 优化脑循环，赋予神经保护的有效手段，从而提高 急性心肌梗死患者的认知功能。已发现间歇性羟色胺可促进神经保护、神经可塑性、 促进神经再生，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，通过动员神经保护性生长/营养因子和通过 改善脑循环，间歇性高血压有望成为预防和/或逆转的有力干预手段 认知衰退和神经退行性进展为阿尔茨海默病。提出具体目标是为了 确认一项为期8周的改善患者神经认知功能的IHT计划的安全性和有效性 并证明间歇性高血压在静息和运动中改善脑血管功能的能力。 精神、生理和低氧挑战，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，因为这将是 希望开发一种特定的、实用的干预措施的研究连续体 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变。 最终，这项调查有望促进新的预防和干预措施的发展。 治疗轻度认知障碍和阿尔茨海默病。

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.