Age Associated Sleep Loss: A Trigger For Alzheimer's Disease

ABSTRACT

Alzheimer's disease (AD) is an untreatable, multifactorial, chronic, progressive, neurodegenerative disorder, which is the principal cause of dementia throughout the world and the fourth most important cause of death in developed economies after cancer, cardiovascular diseases, and vascular stroke. The so-called Alzheimer's epidemic inevitably represents a major health problem to most nations, because there is no effective cure or preventive measure. Present cholinergic and glutamatergic drugs for the treatment of AD are largely symptomatic with temporary clinical benefits regarding cognitive, functional and behavioral manifestations of the disease but with no effect on its progression. Thus, there is a crucial need to discover new and efficient therapeutic strategies. Targeting behavioral aspects of AD represents an approach that may bear fruit, taking a cue from the success of cholinergic treatments in AD. Loss of sleep is a common problem associated with aging and with AD in particular. Clinical evidence has showed that people who suffer from chronic insomnia are about 11 times more likely to develop Alzheimer's disease in later life. Sleep, a behavioral state exhibited by nearly all species, is common in the animal kingdom and has been well preserved in the course of evolution. Sleep is widely considered to be instrumental in maintaining health and cognitive functions. It is a major modulator of several developmental processes including hormone release, glucose regulation, cardiovascular functions, neurogenesis, immune functions, and physiologic balance and resilience. Reduced sleep duration and quality appears to be endemic in modern society; it is a stressor affecting the brain in many ways, including loss of memory and cognitive functions. Alzheimer's disease is typically accompanied by daytime sleepiness and napping as well as severe disruption of nighttime sleep patterns; indeed, disruption of nighttime sleep is often cited as the primary reason for institutionalization of patients. In this review, recent and updated evidence linking sleep disruption to pathological factors playing a decisive role in the progression of Alzheimer's disease is discussed.

Keywords:

• Alzheimer's disease
• amyloid β
• cytokines
• excitotoxicity
• hippocampus
• sleep