Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease

Adv Nutr. 2016 Jul 15;7(4):679-89. doi: 10.3945/an.115.011775. Print 2016 Jul.


Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD.

Keywords: Alzheimer disease; Western diet; acidosis; cortisol; glymphatic system; hippocampus; nutritional interventions; sleep; supplements.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism*
  • Circadian Rhythm
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / prevention & control*
  • Feeding Behavior
  • Humans
  • Hydrocortisone / metabolism*
  • Sleep Wake Disorders / diet therapy*
  • Sleep Wake Disorders / metabolism
  • Sleep*
  • Wakefulness


  • Amyloid beta-Peptides
  • Hydrocortisone