Title:Neurobehavioral and Cognitive Changes Induced by Hypoxia in Healthy Volunteers
Volume: 15
Issue: 7
Author(s): Laura Lanteaume, Catherine Cassé-Perrot, Marie-Noëlle Lefebvre, Christine Audebert, Julie Deguil, Alexandra Auffret, Lisa Otten, David Bartrés-Faz, Olivier Blin, Régis Bordet and Joëlle Micallef
Affiliation:
Keywords:
Alzheimer disease, clinical trial, cognition, cognitive challenge model, compensatory mechanism, healthy
volunteers, hypoxia.
Abstract: The early assessment of new symptomatic drugs against Alzheimer’s disease remains
difficult because of the lack of a predictive end-point. The use of a battery including different
parameters could improve this early development. In order to test the reverse effect of symptomatic
drugs in healthy volunteers, scientists have developed new experimental paradigms to artificially induce
transient cognitive impairments in healthy volunteers akin to those observed in Alzheimer’s disease, i.e.
Cognitive Challenge Models. In this context, transient hypoxia could be a relevant Cognitive Challenge
Model. The deleterious effects of hypoxia on cognition, as described in the literature, should be
considered carefully since they are usually assessed with different populations that do not have the same
hypoxic sensitivity. Hypoxia can be obtained by the means of two different methods: normobaric and
hypobaric hypoxia. In both designs, cognitive changes can be directly modulated by the severity of
hypoxic levels. The purpose of this review is to gather existing support on the application of hypoxia
within different cognitive domains and to highlight the scientific interests of such a model to predict and
select promising drug candidates. We aimed at reviewing in detail the methods, designs and cognitive
paradigms used in non-pharmacological hypoxia studies. Probing the four main cognitive functions will
allow identifying the extent to which different hypoxia designs selectively compromise cognitive
functioning. For each cognitive process, the convergent and divergent results are discussed in terms of
paradigm differences whereas we will focus on defining the optimal methodology for obtaining the
desired effects.
