Reciprocal Interactions Between Sleep, Circadian Rhythms and Alzheimer's Disease: Focus on the Role of Hypocretin and Melatonin

Ageing Res Rev. 2013 Jan;12(1):188-200. doi: 10.1016/j.arr.2012.04.003. Epub 2012 Apr 30.


AD, sleep and circadian rhythm physiology display an intricate relationship. On the one hand, AD pathology leads to sleep and circadian disturbances, with a clear negative influence on quality of life. On the other hand, there is increasing evidence that both sleep and circadian regulating systems exert an influence on AD pathology. In this review we describe the impairments of both sleep regulating systems and circadian rhythms in AD and their link to clinical symptoms, as this may increase knowledge on appropriate diagnosis and adequate treatment of sleep problems in AD. Furthermore we discuss how sleep regulating systems, and especially neurotransmitters such as melatonin and hypocretin, may affect AD pathophysiology, as this may provide a role for lack of sleep and circadian rhythm deterioration in the onset of AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / psychology*
  • Circadian Rhythm / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Melatonin / metabolism
  • Melatonin / physiology*
  • Neuropeptides / metabolism
  • Neuropeptides / physiology*
  • Orexins
  • Sleep / physiology*
  • Sleep Wake Disorders / etiology
  • Sleep Wake Disorders / physiopathology


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Melatonin