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

April 2, 2026 updated by: University of Bern

Preventing Cognitive Decline Using Portable, Non-invasive Sleep Enhancement

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Switzerland
      • Bern, Switzerland, 3000 60
        • Recruiting
        • University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern
        • Contact:
        • Contact:
        • Principal Investigator:
          • Marc A Züst, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PLAS first, sham second
In this study arm, participants will undergo a 4-week intervention period with real phase-locked auditory stimulation (PLAS) administered on nights from Monday to Friday. Following this initial intervention period, participants will have a 2-week washout phase. Finally, participants will enter the second intervention period, during which sham (soundless) PLAS will be administered.
Other: Phase-locked auditory stimulation (PLAS)

Intervention: Verum Phase-Locked Auditory Stimulation (PLAS) Using the SleepLoop Device.

The experimental intervention utilizes the SleepLoop device, a home-use, EEG-based system designed for phase-locked acoustic stimulation (PLAS). The device continuously monitors sleep through EEG (Fpz) alongside electrooculogram (EOG) and electromyogram (EMG) channels. The device employs a closed-loop algorithm that detects slow oscillations (SOs) in the EEG and delivers short sound stimuli (50 ms pink noise) during the positive half-waves of slow waves in slow-wave sleep (SWS). These stimuli are delivered through integrated headphones in the SleepLoop device. The intervention is applied during work days for 4 weeks. The algorithm is only active during SWS and does not deliver stimuli when the participant is awake, or in lighter sleep stages (N1, N2) or REM sleep. The intensity and algorithm sensitivity are individually calibrated for each participant to optimize stimulation.

Other Names:
  • Acoustic stimulation
  • Phase-targeted auditory stimulation (PTAS)
  • Auditory stimulation
  • Closed-loop acoustic stimulation
Other: Sham Phase-Locked Auditory Stimulation
Participants will undergo the same procedure as the real Phase-Locked Auditory Stimulation (PLAS) intervention. However, during the sham condition, the headphones are turned off, and no auditory stimulation is delivered.
Experimental: Sham first, PLAS second
In this study arm, participants will undergo a 4-week intervention period with sham (soundless) phase-locked auditory stimulation (PLAS) administered on nights from Monday to Friday. Following this initial intervention period, participants will have a 2-week washout phase. Finally, participants will enter the second intervention period, during which real PLAS will be administered.
Other: Phase-locked auditory stimulation (PLAS)

Intervention: Verum Phase-Locked Auditory Stimulation (PLAS) Using the SleepLoop Device.

The experimental intervention utilizes the SleepLoop device, a home-use, EEG-based system designed for phase-locked acoustic stimulation (PLAS). The device continuously monitors sleep through EEG (Fpz) alongside electrooculogram (EOG) and electromyogram (EMG) channels. The device employs a closed-loop algorithm that detects slow oscillations (SOs) in the EEG and delivers short sound stimuli (50 ms pink noise) during the positive half-waves of slow waves in slow-wave sleep (SWS). These stimuli are delivered through integrated headphones in the SleepLoop device. The intervention is applied during work days for 4 weeks. The algorithm is only active during SWS and does not deliver stimuli when the participant is awake, or in lighter sleep stages (N1, N2) or REM sleep. The intensity and algorithm sensitivity are individually calibrated for each participant to optimize stimulation.

Other Names:
  • Acoustic stimulation
  • Phase-targeted auditory stimulation (PTAS)
  • Auditory stimulation
  • Closed-loop acoustic stimulation
Other: Sham Phase-Locked Auditory Stimulation
Participants will undergo the same procedure as the real Phase-Locked Auditory Stimulation (PLAS) intervention. However, during the sham condition, the headphones are turned off, and no auditory stimulation is delivered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Episodic memory performance differences (between and within subject) according to the experimental condition
Time Frame: 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.
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.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Electrophysiological Response - Event-Related Potentials (ERPs)
Time Frame: 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.
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 Response - Power, Number, and Amplitude of Slow Oscillations (SO) and Spindles
Time Frame: 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.
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 Response - Coupling of Slow Oscillations and Sleep Spindles
Time Frame: 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.
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.
Amyloid-Beta Response
Time Frame: 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.
At baseline, after 4 weeks, after 6 weeks, after 10 weeks
Electrophysiology - Brain Age Estimation
Time Frame: 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.
Sleep electrophysiology will be measured on weekdays during the adaptation week and on weekdays throughout both the first and second 4-week intervention periods.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Bern

Collaborators

University of Zurich
Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)

Investigators

  • Principal Investigator: Marc A Züst, PhD, University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, 3000 Bern, Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2025

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

October 29, 2024

First Submitted That Met QC Criteria

October 30, 2024

First Posted (Actual)

November 1, 2024

Study Record Updates

Last Update Posted (Actual)

April 3, 2026

Last Update Submitted That Met QC Criteria

April 2, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-00409
  • 215333 (Other Grant/Funding Number: Swiss National Science Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Currently, there are no collaborations to disclose, but the investigators are generally open to such endeavours in the future. For this purpose, general consent for reuse of data is being collected from participants.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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