Fig. 1

Schematic of sleep disturbances in Alzheimer’s disease. Sleep is subdivided into stages of rapid eye movement (REM) and non-REM (NREM) sleep by signatures of neuronal activity. NREM can be further subdivided into 3 stages; NREM stage 3 is often referred to as slow wave sleep (SWS). a In healthy individuals, sleep begins in NREM stage 1, with waning neuronal activity and frequency, which further slows in restorative NREM stage 2 and SWS. SWS dominates early in the sleep cycle with synchronous, low frequency delta waves, whereas transitions to REM sleep occur a few hours after sleep onset, in ~ 90-min cycles. REM sleep electroencephalogram (EEG) is more akin to wakefulness with higher frequency and lower amplitude signals than SWS and dominated by theta waves. Memory consolidation is facilitated by bouts of REM, as well as NREM stage 2, prominent late in the sleep cycle, with characteristic high amplitude K-complexes and high frequency sleep spindles in EEG. In summary, REM and NREM stage 2 and 3 are important in memory consolidation [65,66,67,68]; whereas SWS is also critical for toxic protein clearance and to reduce net synaptic strength to dampen aberrant plasticity and preserve a healthy signal:noise ratio of neuronal activity [68, 69]. Individuals who experience sleep disturbances are at a higher risk for Alzheimer’s disease (AD), and, moreover, those with AD exhibit characteristic features of sleep loss. b In AD, sleep is disrupted throughout the night, in which there is a delayed onset, longer bouts of non-restorative NREM stage 1 sleep, reduced bouts of SWS, REM and NREM stage 2, as well as increased wakefulness (notable changes compared to healthy sleep are circled). In sum, sleep disturbance poses a significant risk for AD and other neurodegenerative diseases, most prominently through dysregulation of mechanisms that facilitate proteinopathy and cognitive deficits (see Fig. 3). Panels A and B are schematic representations of healthy sleep and common disturbances that occur in AD. Healthy control sleep stages were informed from [68], and the results of the meta-analysis in [22] informed the AD impairments demonstrated in panel B