Sleep and Alzheimer disease pathology-a bidirectional relationship

Factors other than age and genetics may increase the risk of developing Alzheimer disease (AD). Accumulation of the amyloid-beta (A beta) peptide in the brain seems to initiate a cascade of key events in the pathogenesis of AD. Moreover, evidence is emerging that the sleep-wake cycle directly influences levels of A beta in the brain. In experimental models, sleep deprivation increases the concentration of soluble A beta and results in chronic accumulation of A beta, whereas sleep extension has the opposite effect. Furthermore, once A beta accumulates, increased wakefulness and altered sleep patterns develop. Individuals with early A beta deposition who still have normal cognitive function report sleep abnormalities, as do individuals with very mild dementia due to AD. Thus, sleep and neurodegenerative disease may influence each other in many ways that have important implications for the diagnosis and treatment of AD.