Acoustic enhancement of sleep slow oscillations in mild cognitive impairment

Abstract

Objective Slow‐wave activity (SWA) during sleep is reduced in people with amnestic mild cognitive impairment (aMCI) and is related to sleep‐dependent memory consolidation. Acoustic stimulation of slow oscillations has proven effective in enhancing SWA and memory in younger and older adults. In this study we aimed to determine whether acoustic stimulation during sleep boosts SWA and improves memory performance in people with aMCI. Methods Nine adults with aMCI (72 ± 8.7 years) completed one night of acoustic stimulation (stim) and one night of sham stimulation (sham) in a blinded, randomized crossover study. Acoustic stimuli were delivered phase‐locked to the upstate of the endogenous sleep slow‐waves. Participants completed a declarative recall task with 44 word‐pairs before and after sleep. Results During intervals of acoustic stimulation, SWA increased by >10% over sham intervals (P < 0.01), but memory recall increased in only five of the nine patients. The increase in SWA with stimulation was associated with improved morning word recall (r = 0.78, P = 0.012). Interpretation Acoustic stimulation delivered during slow‐wave sleep over one night was effective for enhancing SWA in individuals with aMCI. Given established relationships between SWA and memory, a larger or more prolonged enhancement may be needed to consistently improve memory in aMCI.

Local Sleep and Alzheimer’s Disease Pathophysiology

“…Hence, optogenetic manipulation of both SO and sleep spindle events directly impacts long-term memory retention, supporting their causal role in sleep-dependent memory consolidation. This model is further supported by studies that mechanistically enhance slow waves, sleep spindles, and slow wave-sleep spindle coupling through external electrical and auditory stimulation methods in humans, resulting in improved procedural and episodic memory, even in older adults and patients with MCI (Marshall et al, 2004(Marshall et al, , 2006Westerberg et al, 2015;Lustenberger et al, 2016;Ladenbauer et al, 2017;Papalambros et al, 2017Papalambros et al, , 2019.…”

“…While there are some data that suggest that treating sleep disorders may impact AD biomarkers ( Osorio et al, 2015 ; Liguori et al, 2017a , b ), large scale studies are lacking. Further, while a few reports show that enhancing local sleep in older adults and patients with MCI will improve overnight memory consolidation ( Ladenbauer et al, 2017 ; Papalambros et al, 2019 ), the efficacy of this type of intervention, even for more than one night, is unknown. As important is an examination of the impact of AD disease stage on the efficacy of sleep interventions to impact AD pathophysiology and related cognitive impairments.…”

Characteristics of Sleep Structure Assessed by Objective Measurements in Patients With Amnestic Mild Cognitive Impairment: A Meta-Analysis

“…Memory impairment in aging is also indicated to be related to suppressed slow waves (41,42). A trial demonstrated that enhancing slow wave activity conducted by acoustic stimulation was associated with improved morning word recall in individuals with aMCI (43). Accumulation of amyloid-β and tau aggregates, two histopathological markers of AD in the brain, are demonstrated to correlate with decreased SWS (44).…”

The Treatment of Sleep Dysfunction in Neurodegenerative Disorders

“…There has to date been only one study of acoustic augmentation of SWS in a neurodegenerative cohort [227]. Conducted in 2019, this nocturnal pilot study in nine patients with amnestic mild cognitive impairment demonstrated highly variable increases in slow-wave activity (1-30%), but promisingly, improvement in declarative memory was demonstrated in five of nine participants, and the degree of improvement correlated with that of slow-wave activity augmentation.…”