To this day, the pharmacological treatment of Alzheimer’s disease
remains limited to the temporary stabilisation of cognitive decline and the reduction
of neuropsychiatric symptoms. It is moreover with great difficulty to predict and
select promising drug candidates in the early stages of the discovery and
developmental process. In this context, 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. the Cognitive Challenge Models.
In the last decade, a great amount of literature on Sleep Deprivation was published
which mainly focused on the consequences of sleep loss for public health. However,
sleep deprivation paradigm may also be regarded as a cognitive challenge model. It
is commonly accepted that sleep deprivation induces cognitive impairments related to a global decrease
in vigilance, while in fact, there is a controversial approach related to the selective effects on cognitive
functions. The identification and validation of cognitive challenge models in healthy volunteers are
suitable in early clinical development of drugs to determine the ‘hint of efficacy’ of drug candidates.
The present review aims at exploring in detail the methods, designs and cognitive paradigms used in
non pharmacological sleep deprivation studies. Sleep deprivation can be induced by different methods.
Probing the four main cognitive functions will allow identifying the extent to which different sleep
deprivation designs selectively compromise executive function, working memory, episodic memory and
attention. Findings will be discussed in line with cognitive processing levels that are required according
to the tasks.
Keywords: Alzheimer disease, cognitive functioning, cognitive tests, compensatory mechanism, healthy volunteers, model,
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