Altitude-like cognition training to promote neuroplasticity and cognitive functions

Cognitive impairment is a debilitating feature of psychiatric disorders linked to decreased neuroplasticity. Moderate hypoxia is increasingly recognised as a key physiological driver of neuroprotection and -regeneration. Two parallel randomised controlled proof-of-concept studies investigated the efficacy of cognitive training under moderate hypoxia (H-CT) for 3.5 hours, repeated 5-6 days per week over three weeks. In the first sub-study, 126 healthy volunteers were randomised to one of four treatment arms in a double-blind manner to investigate separate and combined effects of hypoxia and cognitive training. In the second sub-study, 64 individuals with clinically stable mood disorders and cognitive impairment were randomised to H-CT or treatment as usual in an assessor-blinded design. The primary outcome was a composite measure of executive functions, memory, and attention. Additional cognitive, functioning, neuroimaging (SV2A as a presynaptic marker with [11C]UCB-J PET and neural activity during working memory fMRI), and blood-based outcomes were assessed. In healthy individuals, H-CT improved the primary outcome with a delayed onset of effect one month post-treatment. In contrast, cognitive training alone produced only immediate cognitive improvement that did not prevail after one month. In the clinical study, H-CT produced selective improvements in executive functions, better everyday functioning, and more efficient recruitment of the dorsal prefrontal cortex during fMRI. In both sub-studies, cognitive gains were accompanied by H-CT-related lower presynaptic [11C]UCB-J binding in subcortical regions. During the symposium, Viktoria Damgaard will present these findings and discuss the potential of moderate hypoxia as a non-invasive add-on therapeutic strategy for cognitive impairment in psychiatry.