Age associated sleep loss: a trigger for Alzheimer's disease

Abstract

Alzheimer s disease (AD) is an untreatable, multifactorial, chronic, progressive, neurodegenerativedisorder, which is the principal cause of dementia throughout the world and the fourth mostimportant cause of death in developed economies after cancer, cardiovascular diseases, andvascular stroke. The so-called Alzheimer s epidemic inevitably represents a major health problemto most nations, because there is no effective cure or preventive measure. Present cholinergicand glutamatergic drugs for the treatment of AD are largely symptomatic with temporary clinicalbenefits regarding cognitive, functional and behavioral manifestations of the disease but with noeffect on its progression. Thus, there is a crucial need to discover new and efficient therapeuticstrategies. Targeting behavioral aspects of AD represents an approach that may bear fruit, takinga cue from the success of cholinergic treatments in AD. Loss of sleep is a common problemassociated with aging and with AD in particular. Clinical evidence has showed that people whosuffer from chronic insomnia are about 11 times more likely to develop Alzheimer s diseasein later life. Sleep, a behavioral state exhibited by nearly all species, is common in the animalkingdom and has been well preserved in the course of evolution. Sleep is widely consideredto be instrumental in maintaining health and cognitive functions. It is a major modulator ofseveral developmental processes including hormone release, glucose regulation, cardiovascularfunctions, neurogenesis, immune functions, and physiologic balance and resilience. Reducedsleep duration and quality appears to be endemic in modern society; it is a stressor affectingthe brain in many ways, including loss of memory and cognitive functions. Alzheimer s diseaseis typically accompanied by daytime sleepiness and napping as well as severe disruption ofnighttime sleep patterns; indeed, disruption of nighttime sleep is often cited as the primaryreason for institutionalization of patients. In this review, recent and updated evidence linkingsleep disruption to pathological factors playing a decisive role in the progression of Alzheimer sdisease is discussed.