Clinical trial NCT06669546: 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
Official title: Preventing Cognitive Decline Using Portable, Non-invasive Sleep Enhancement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cognitive Decline
Alzheimer Disease
Subjective Cognitive Decline (SCD)
Mild Cognitive Impairment (MCI)
Cognitive Impairment, Mild
Keywords: Sleep
Dementia
Prevention
Phase-locked auditory stimulation
Blood-based biomarkers
Home
Longitudinal
Electroneurophysiology
EEG
Memory
Cognition
Serious games
Old age
Human
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: University of Zurich
name: Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
First posted: 2024-11-01
Enrollment: 60
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Episodic memory performance differences (between and within subject) according to the experimental condition
timeFrame: 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 outcomes:
measure: Electrophysiological Response - Event-Related Potentials (ERPs)
timeFrame: 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.
measure: Electrophysiological Response - Power, Number, and Amplitude of Slow Oscillations (SO) and Spindles
timeFrame: 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.
measure: Electrophysiological Response - Coupling of Slow Oscillations and Sleep Spindles
timeFrame: 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.
measure: Amyloid-Beta Response
timeFrame: At baseline, after 4 weeks, after 6 weeks, after 10 weeks
measure: Electrophysiology - Brain Age Estimation
timeFrame: Sleep electrophysiology will be measured on weekdays during the adaptation week and on weekdays throughout both the first and second 4-week intervention periods.
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern
Study officials:
affiliation: University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, 3000 Bern, Switzerland
name: Marc A Züst, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lustenberger C, Ferster ML, Huwiler S, Brogli L, Werth E, Huber R, Karlen W. Auditory deep sleep stimulation in older adults at home: a randomized crossover trial. Commun Med (Lond). 2022 Apr 4;2:30. doi: 10.1038/s43856-022-00096-6. eCollection 2022.
citation: Wunderlin M, Zust MA, Hertenstein E, Feher KD, Schneider CL, Kloppel S, Nissen C. Modulating overnight memory consolidation by acoustic stimulation during slow-wave sleep: a systematic review and meta-analysis. Sleep. 2021 Jul 9;44(7):zsaa296. doi: 10.1093/sleep/zsaa296.
citation: Zeller CJ, Wunderlin M, Wicki K, Teunissen CE, Nissen C, Zust MA, Kloppel S. Multi-night acoustic stimulation is associated with better sleep, amyloid dynamics, and memory in older adults with cognitive impairment. Geroscience. 2024 Dec;46(6):6157-6172. doi: 10.1007/s11357-024-01195-z. Epub 2024 May 14.
citation: Wunderlin M, Zeller CJ, Senti SR, Feher KD, Suppiger D, Wyss P, Koenig T, Teunissen CE, Nissen C, Kloppel S, Zust MA. Acoustic stimulation during sleep predicts long-lasting increases in memory performance and beneficial amyloid response in older adults. Age Ageing. 2023 Dec 1;52(12):afad228. doi: 10.1093/ageing/afad228.