Balmeet Toor^a, Laura B. Ray^{a, b}, Alyssa Pozzobon^a, Stuart M. Fogel^a–c

^a School of Psychology, University of Ottawa, Ottawa, ON, Canada; 
^b Sleep Unit, The Royal’s Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada; 
^c University of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada

© 2021 The Author(s)
Published by S. Karger AG, Basel

• Chapter 4 graphical abstract

Orexins regulate a wide variety of biological functions, most notably the sleep-wake cycle, reward and stress processing, alertness, vigilance, and cognitive functioning. Alterations of central and peripheral orexin levels are linked to conditions such as narcolepsy, anorexia nervosa, age-related cognitive decline, and neurodegenerative disease. Preliminary studies suggest that orexin mimetics can safely promote the wake signal via orexin agonism during the day and that orexin receptor antagonists can promote the sleep signal during the night. Thus, novel orexin therapies have the potential to either improve memory, cognition, and daytime performance directly or indirectly, through promotion of good sleep. The full scope of the therapeutic potential of orexin therapies remains to be elucidated.

• Orexins benefit wakefulness, vigilance, memory, and cognition.
• Orexins regulate various biological functions that indirectly and directly impact memory, cognition, and daytime performance.
• Orexin receptors are a potential novel therapeutic target to improve cognition in sleep disorders, age-related cognitive decline, and neurodegenerative disease.
• The link between orexins, their impact on wakefulness and vigilance, and memory and cognition remains to be thoroughly investigated.

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