Alzheimer’s disease (AD) affects not only the central nervous system, but also peripheral blood cells including neutrophils and platelets, which actively participate in pathogenesis of AD through a vicious cycle between platelets aggregation and production of excessive amyloid beta (Aβ). Platelets adhesion on amyloid plaques also increases the risk of cerebral microcirculation disorders. Moreover, activated platelets release soluble adhesion molecules that cause migration, adhesion/activation of neutrophils and formation of neutrophil extracellular traps (NETs), which may damage blood brain barrier and destroy brain parenchyma. The present study examined the effects of intermittent hypoxic-hyperoxic training (IHHT) on elderly patients with mild cognitive impairment (MCI), a precursor of AD. Twenty-one participants (age 51–74 years) were divided into three groups: Healthy Control (n = 7), MCI+Sham (n = 6), and MCI+IHHT (n = 8). IHHT was carried out five times per week for three weeks (total 15 sessions). Each IHHT session consisted of four cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Cognitive parameters, Aβ and amyloid precursor protein (APP) expression, microRNA 29, and long non-coding RNA in isolated platelets as well as NETs in peripheral blood were investigated. We found an initial decline in cognitive function indices in both MCI+Sham and MCI+IHHT groups and significant correlations between cognitive test scores and the levels of circulating biomarkers of AD. Whereas sham training led to no change in these parameters, IHHT resulted in the improvement in cognitive test scores, along with significant increase in APP ratio and decrease in Aβ expression and NETs formation one day after the end of three-week IHHT. Such effects on Aβ expression and NETs formation remained more pronounced one month after IHHT. In conclusion, our results from this pilot study suggested a potential utility of IHHT as a new non-pharmacological therapy to improve cognitive function in pre-AD patients and slow down the development of AD.

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The present study investigated the beneficial effects of intermittent hypoxia training (IHT) in humans under prediabetic conditions. We found that three-week moderate IHT induced higher HIF-1a mRNA expressions as well as its target genes, which were positively correlated with higher tolerance to acute hypoxia and better glucose homeostasis in both middle-aged healthy and prediabetic subjects. This small clinical trial has provided new data suggesting a potential utility of IHT for management of prediabetes patients. AbstractThe present study aimed at examining beneficial effects of intermittent hypoxia training (IHT) under prediabetic conditions. We investigate the effects of three-week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA expression of hypoxia inducible factor 1a (HIF-1a) and its target genes, i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2, and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic men and women (44-70 years of age) were examined before, next day and one month after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5-min 12% O 2 and 5-min room air breathing). We found that IHT afforded beneficial effects on glucose homeostasis in patients with prediabetes reducing fasting glucose and during standard oral glucose tolerance test. The most pronounced positive effects were observed at one month after IHT termination. IHT also significantly increased the tolerance to acute hypoxia (i.e. SaO 2 level at 20th min of breathing with 12% O 2 ) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1a mRNA expression in blood leukocytes in healthy and prediabetic subjects, but in prediabetes patients the maximum increase was lagged. The greatest changes in mRNA expression of HIF-1a target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1a was positively associated with higher tolerance to hypoxia and better glucose homeostasis. In conclusion, our results suggest that IHT may be useful for preventing the development of type 2 diabetes.

The introduction of different methods of intermittent hypoxic training (IHT) into fitness

Several studies have assessed the effects of intermittent hypoxia-normoxia training (IHNT), intermittent hypoxia-hyperoxia training (IHHT), and obstructive sleep apnea (OSA) on aging and age-related diseases in humans; however, the results remain contradictory. Therefore, this review aims to systematically summarize the available studies on the effects of IHNT, IHHT, and OSA on aging and age-related diseases. Relevant studies were searched from PubMed, Google Scholar, Cochrane Library databases, and through manual searching from reference lists of eligible studies. A total of 38 eligible studies were included in this systematic review. IHHT and IHNT provide positive effects on several age-related parameters including quality of life, cognitive and physical functions, plasma level of glucose and cholesterol/LDL, systolic blood pressure, red blood cells, and inflammation. Moreover, moderate intermittent hypoxia induces telomerase reverse transcriptase (TERT) activity and telomere stabilization, delays induction of senescence-associated markers expression and senescence-associated β-galactosidase, upregulates pluripotent marker (Oct4), activates a metabolic shift, and raises resistance to pro-apoptotic stimuli. On the contrary, intermittent hypoxia in OSA causes hypertension, metabolic syndrome, vascular function impairment, quality of life and cognitive scores reduction, advanced brain aging, increase in insulin resistance, plasma hydrogen peroxide, GSH, IL-6, hsCRP, leptin, and leukocyte telomere shortening. Thus, it can be speculated that the main factor that determines the direction of the intermittent hypoxia action is the intensity and duration of exposure. There is no direct study to prove that IHNT/IHHT actually increases life expectancy in humans. Therefore, further study is needed to investigate the actual effect of IHNT/IHHT on aging in humans.Systematic Review Registrationwww.crd.york.ac.uk/prospero, identifier CRD42022298499.