Acoustic Stimulation to Improve Slow-Wave Sleep in Alzheimer's Disease: a Multiple Night At-Home Intervention

Objectives To investigate the efficacy of closed-loop acoustic stimulation (CLAS) during slow-wave sleep (SWS) to enhance slow-wave activity (SWA) and SWS in patients with Alzheimer's disease (AD) across multiple nights and to explore associations between stimulation, participant characteristics, and individuals’ SWS response. Design A two-week, open-label at-home intervention study utilizing the DREEM2 headband to record sleep data and administer CLAS during SWS. Setting and participants Fifteen older patients with AD (6 women, mean age: 76.27 (SD=6.06), mean MOCA-score: 16.07 (SD=6.94)), living at home with their partner, completed the trial. Intervention Patients first wore the device for two baseline nights, followed by 14 nights during which the device was programmed to randomly either deliver acoustic stimulations of 50ms pink noise (± 40 dB) targeted to the slow-wave up-phase during SWS or only mark the wave (sham). Results On a group level, stimulation significantly enhanced SWA and SWS with consistent SWS enhancement throughout the intervention. However, substantial variability existed in individual responses to stimulation. Individuals received more stimulations on nights with increased SWS compared to baseline than on nights with no change or a decrease. In individuals, having lower baseline SWS correlated with receiving fewer stimulations on average during the intervention. Conclusion CLAS during SWS is a promising non-pharmacological method to enhance SWA and SWS in AD. However, patients with lower baseline SWS received fewer stimulations during the intervention, possibly resulting in less SWS enhancement. Individual variability in response to stimulation underscores the need to address personalized stimulation parameters in future research and therapy development.