Unraveling the contributions of sleep dysfunction to Alzheimer's disease

Abstract Sleep disturbances are common in dementia, including dementia due to Alzheimer's disease (AD). The discovery of the glymphatic system, optimized during sleep, has propelled interest in the role of sleep in amyloid beta dynamics and AD pathophysiology. Mechanistic studies suggest that both wakefulness and disrupted slow-wave sleep relate to an acute increase in amyloid beta. However, it remains unclear whether sleep disturbances contribute to the development of amyloid beta oligomers and the downstream changes that contribute to clinical dementia. Prospective community-based cohort studies have pointed toward the importance of REM rather than slow-wave sleep as a predictor of cognitive decline and incident dementia. Discordance between mechanistic and cohort studies suggests a complex interplay between sleep and the development of AD dementia. Further studies are required to elucidate the multifaceted relationships between sleep and AD with exploration of mechanisms beyond the role of slow-wave sleep in amyloid accumulation.