Exploring the nexus: Sleep disorders, circadian dysregulation, and Alzheimer’s disease

Abstract

We reviewed the connections among Alzheimer’s disease (AD), sleep deprivation, and circadian rhythm disorders. Evidence is mounting that disrupted sleep and abnormal circadian rhythms are not merely symptoms of AD, but are also involved in accelerating the disease. Amyloid-beta (Aβ) accumulates, a feature of AD, and worsens with sleep deprivation because glymphatic withdrawal is required to clear toxic proteins from the brain. In addition, disturbances in circadian rhythm can contribute to the induction of neuroinflammation and oxidative stress, thereby accelerating neurodegenerative processes. While these interactions are bidirectional, Alzheimer’s pathology further disrupts sleep and circadian function in a vicious cycle that worsens cognitive decline, which is emphasized in the review. The evidence that targeting sleep and circadian mechanisms may serve as therapeutic strategies for AD was strengthened by this study through the analysis of the molecular and physiological pathways. Further work on this nexus could help unravel the neurobiological mechanisms common to the onset of Alzheimer’s and disrupted sleep and circadian regulation, which could result in earlier intervention to slow or prevent the onset of the disease.