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

Официальное название

Preventing Cognitive Decline Using Portable, Non-invasive Sleep Enhancement

Обзор

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.

Вмешательства

• Другое 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 nois
• Другое 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.

Первичные конечные точки

• Episodic memory performance differences (between and within subject) according to the experimental condition [Срок оценки: 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.]

Вторичные конечные точки (5)

• Electrophysiological Response - Event-Related Potentials (ERPs) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: At baseline, after 4 weeks, after 6 weeks, after 10 weeks]
• Electrophysiology - Brain Age Estimation [Срок оценки: Sleep electrophysiology will be measured on weekdays during the adaptation week and on weekdays throughout both the first and second 4-week intervention periods.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

Швейцария · 1 центр

• University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern — Bern

Публикации

• 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. PMID 35603302
• 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. PMID 33406249
• 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. PMID 38744792
• 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. PMID 38163288

Идентификаторы

NCT: NCT06669546 · 2024-00409 · 215333

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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