Intermittent Hypoxia Training: A Novel Therapy for Mild Cognitive Impairment

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.