RETRACTED: Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer’s Disease in Patients with Mild Cognitive Impairment: A Pilot Study

Abstract

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.

Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets

“…Although hypoxia may trigger a vicious cycle of events including mitochondrial dysregulation, acidosis, altered mitochondrial membrane permeability, and eventually insufficiency of ATP biosynthesis [68], certain moderate types/degrees of hypoxia can induce an adaptive phenomenon called "hypoxic conditioning" or "hypoxic preconditioning", which would act as a vaccine to protect against hypoxia-induced lethal damages in various organs and cells. Such hypoxic signals can be generated via a wellcontrolled intermittent hypoxia-normoxia or hypoxia-hyperoxia training program by means of (1) inhalation of low oxygen gas mixtures; (2) staying in hypobaric chambers, and (3) recurrent sojourn at high altitudes [69][70][71][72].…”

Adaptation to Hypoxia: A Chimera?

“…A novel modification of the IHC paradigm, intermittent hypoxic-hyperoxic training (IHHT), consisting in four cycles of five minutes of hypoxia (12% FIO 2 ) and three minutes of hyperoxia (33% FIO 2 ), five times per week for three weeks (for a total of 15 sessions), improves cognitive test scores, along with a significant increase in amyloid precursor protein and decrease in amyloid beta expression and adhesion/activation of neutrophils in elderly patients with mild cognitive impairment. Serebrovska et al [11] thus suggest a potential utility of IHHT as a new non-pharmacological therapy to improve cognitive function in pre-Alzheimer's disease patients and slow down the development of Alzheimer's disease.…”

Mithridatism for dementia? Hypoxic - Hyperoxic training in dementia

“…These effects on Aβ expression and NETs formation remained more pronounced one month after IHHT. In conclusion, the results from this pilot study suggested a potential usage of IHHT as a new therapy to improve cognitive function in pre-AD patients and slow down the development of AD (Serebrovska et al, 2019).…”

“…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. (Serebrovska et al, 2019) The study found an initial decline in cognitive function indices in both MCI+Sham and MCI+IHHT groups and important connections between cognitive test scores and the levels of circulating biomarkers of AD. 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.…”

“…Hypoxia regulates metapolyzing amyloid plaque protein (APP), causing a growing production of Aβ through the amyloidogenic mechanism. Time-reliant hypoxic upregulation of APP has been further proven at the mRNA and protein levels, following 10-180 mins of ischemia, which might function as a guarding pathway to raise the levels of neuroprotective soluble APPα (Serebrovska et al, 2019). Yet, most times the growing APP leads to more levels of Aβ, not soluble APPα since hypoxia prefers metapolizing APP through the amyloidogenic mechanism (Urike Bayer et al, 2017)…”