Effects of Real vs. Soundless Acoustic Stimulation During Deep Sleep on Brain Activity, Memory, and Blood Biomarkers in Older Adults (60-85) With Mild Memory Impairment

Not Applicable

Recruiting

• Conditions: Cognitive Decline; Alzheimer Disease; Subjective Cognitive Decline (SCD); Mild Cognitive Impairment (MCI); Cognitive Impairment, Mild

• Registration Number: NCT06669546
• Lead Sponsor: University of Bern

Brief Summary

This study aims to explore a non-invasive way to improve memory and slow cognitive decline in older adults by enhancing sleep quality. Dementia, a leading cause of death worldwide, is often associated with disturbed sleep, particularly the loss of deep, slow-wave sleep (SWS). SWS is important for memory and clearing waste from the brain. Poor SWS can worsen memory loss and allow harmful waste to build up, which may increase the risk of dementia.

The investigators are testing whether phase-locked auditory stimulation (PLAS) can improve SWS in people at a mild stage of cognitive impairment. PLAS uses short sounds played at specific moments to strengthen slow-wave brain activity during sleep. The investigators previous laboratory based research has shown that this can improve memory and help with clearing waste from the brain. Now, the investigators want to test this in a real-world setting, over a longer period, which is unfeasible in a laboratory setting.

In this study, 60 older adults will use home-use devices that deliver either real or sham (soundless) PLAS across two different 4-week periods. Memory will be tested using engaging "serious games." Before and after each experimental period, blood samples will be taken to measure dementia-related markers, and cognitive batteries will be performed. The investigators expect that PLAS will improve sleep, and that this will have a downstream effect on memory and brain clearance, potentially slowing the process of cognitive decline.

If successful, this could lead to the development of an affordable treatment that helps people maintain brain health and prevent dementia.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-10-29
• Study First Submitted QC: 2024-10-30
• Study First Posted: 2024-11-01
• Study Start: 2025-02-21
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Primary Completion: 2028-05
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Written informed consent
• Age between 60 and 85 years
• Cognitive impairment (subjective and/or MoCA between 23-26)
• Native German speakers or comparably fluent
• Normal or corrected-to-normal vision.
• Intact hearing
• A close cohabitant (partner/sibling) should be present to support participants in using study materials/devices.

Exclusion Criteria

• Insomnia assessed by the Regensburg Insomnia Scale (RIS; Crönlein et al., 2013)
• Restless leg syndrome assessed by questions concerning typical symptoms.
• Sleep apnoea assessed by the Berlin Questionnaire (BQ; Netzer et al., 1999)
• Severely irregular sleep patterns assessed by the RIS and the Pittsburgh sleep quality index (PSQI; Buysse et al., 1989)
• Symptoms of depression (Geriatric Depression Scale (GDS; Yesavage et al., 1982) ≥ 5)
• History of untreated severe neurological and psychiatric diseases
• Alcohol or substance abuse
• Use of medication acting on the central nervous system

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Episodic memory performance differences (between and within subject) according to the experimental condition	Participants will play serious games on weekdays during the adaptation week, as well as on weekdays throughout both the first and second 4-week intervention periods.	Episodic memory performance will be assessed by means of serious games.

Secondary Outcome Measures

Name	Time	Method
Electrophysiological Response - Event-Related Potentials (ERPs)	Sleep-Electrophysiology will be measured on weekdays during the adaptation week, as well as on weekdays throughout both the first and second 4-week intervention periods.	Electrophysiological responses will be measured via EEG to assess event-related potentials (ERPs) in response to real versus sham acoustic stimulation.
Electrophysiological Response - Power, Number, and Amplitude of Slow Oscillations (SO) and Spindles	Sleep-electrophysiology will be measured on weekdays during the adaptation week, as well as on weekdays throughout both the first and second 4-week intervention periods.	Electrophysiological responses will be measured via EEG to assess the power, number, and amplitude of slow oscillations (SO) and sleep spindles in response to real versus sham acoustic stimulation.
Electrophysiological Response - Coupling of Slow Oscillations and Sleep Spindles	Sleep-electrophysiology will be measured on weekdays during the adaptation week, as well as on weekdays throughout both the first and second 4-week intervention periods.	Electrophysiological responses will be measured via EEG to assess the coupling between slow oscillations and spindles in response to real versus sham acoustic stimulation.
Amyloid-Beta Response	At baseline, after 4 weeks, after 6 weeks, after 10 weeks	Blood samples will be collected to measure plasma amyloid-beta levels and compare them across conditions.
Electrophysiology - Brain Age Estimation	Sleep electrophysiology will be measured on weekdays during the adaptation week and on weekdays throughout both the first and second 4-week intervention periods.	EEG, EMG, and ECG will be used to estimate brain age and assess whether PLAS leads to a rejuvenation of the brain, reflecting a younger brain state. Machine learning will analyze sleep-EEG data to provide an accurate brain age estimate.

Trial Locations

Locations (1)

University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern; 🇨🇭 Bern, Switzerland