Does Acoustic Stimulation During Sleep Boost Slow Wave Sleep and Memory Performance?

Improving Slow Wave Sleep by Auditory Stimulation to Enhance Memory Consolidation and New Learning in Healthy Older Adults and Older Individuals at Risk for Dementia

With aging the amount of slow wave sleep decreases drastically and this disruption is markedly exaggerated in older adults suffering from mild cognitive impairment and Alzheimer's disease. Critically, the disruption of slow wave sleep and cognitive decline seem bidirectionally linked forming a vicious cycle. In the long run, improving slow wave sleep might be a useful intervention tool to delay the onset of cognitive decline. The present study aims at improving slow wave sleep and memory functions through a closed-loop acoustic stimulation approach. A closed-loop algorithm is used that detects slow waves in the electroencephalogram and is programmed to present short tones (50 ms) in the rhythm of these waves. This procedure has shown to boost both slow wave sleep as well as memory performance, mainly in young adults and when applied for one night. Here, the investigators apply tones via multiple consecutive nights and assess memory performance during this 3-night intervention.

Study Overview

• Status: Completed
• Conditions: Healthy; Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Other: Closed loop acoustic stimulation; Other: Sham acoustic stimulation

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3000 60
    • University Hospital of Old Age Psychiatry and Psychotherapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Written informed consent
• Fluent in German
• Normal or corrected to normal vision
• Unimpaired hearing
• For healthy group: Montreal Cognitive Assessment Score ≥ 26
• For MCI group: Montreal Cognitive Assessment Score < 26
• For at risk group: smoker, high cholesterol, high blood pressure and high fasting plasma glucose OR smoker, high BMI, physically inactive, unhealthy dietary habits

Exclusion Criteria:

• Known sleep problems such as Insomnia, restless leg syndrome, apnea
• Irregular sleep pattern
• Symptoms of depression
• History of untreated severe neurological and psychiatric diseases
• Alcohol or substance abuse
• Use of medication acting on the central nervous system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy intervention; Acoustic stimulation	Other: Closed loop acoustic stimulation; The intervention consists of three consecutive nights of closed loop acoustic stimulation during slow wave sleep. An established closed-loop algorithm is utilized that detects slow oscillations in the electroencephalogram and is programmed to present short tones (50 ms) into their up-states. Tones will be presented via a headband with integrated speakers. The procedure does not wake participants
Sham Comparator: Healthy sham; No stimulation	Other: Sham acoustic stimulation; Sham acoustic stimulation: participants wear the headband but no stimuli are delivered during slow wave sleep. This ensures that in both the control and the intervention group the conscious experiences are the same.
Experimental: At risk intervention; Acoustic stimulation	Other: Closed loop acoustic stimulation; The intervention consists of three consecutive nights of closed loop acoustic stimulation during slow wave sleep. An established closed-loop algorithm is utilized that detects slow oscillations in the electroencephalogram and is programmed to present short tones (50 ms) into their up-states. Tones will be presented via a headband with integrated speakers. The procedure does not wake participants
Sham Comparator: At risk sham; No stimulation	Other: Sham acoustic stimulation; Sham acoustic stimulation: participants wear the headband but no stimuli are delivered during slow wave sleep. This ensures that in both the control and the intervention group the conscious experiences are the same.
Experimental: MCI (mild cognitive impairment) intervention; Acoustic stimulation	Other: Closed loop acoustic stimulation; The intervention consists of three consecutive nights of closed loop acoustic stimulation during slow wave sleep. An established closed-loop algorithm is utilized that detects slow oscillations in the electroencephalogram and is programmed to present short tones (50 ms) into their up-states. Tones will be presented via a headband with integrated speakers. The procedure does not wake participants
Sham Comparator: MCI (mild cognitive impairment) sham; No stimulation	Other: Sham acoustic stimulation; Sham acoustic stimulation: participants wear the headband but no stimuli are delivered during slow wave sleep. This ensures that in both the control and the intervention group the conscious experiences are the same.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline episodic memory performance after three nights of intervention	Face-occupation associative memory task: encoding of 40 faces coupled with 40 occupations takes place on the evening of the first intervention night followed by a retrieval session (BASELINE). Feedback-based retrieval sessions take place on the following mornings and evenings of three consecutive intervention nights (4 feedback-based encoding sessions). After the last intervention night a retrieval session without feedback is performed upon waking (ASSESSMENT OF CHANGE)	The change in memory performance will be assessed between the baseline measurement (evening before the first intervention night) and on the morning of the last intervention night (1 hour after waking), 3 days after initial encoding
Change from baseline performance in computer-based verbal new learning task (episodic memory) after three nights of intervention	Verbal associative memory task: a list of 30 moderately associated word pairs (e.g. balloon-air) are presented on a screen. The respective word pairs are displayed for five seconds each and participants are asked to memorize them. After a one-minute break, a cued recall follows in which one word of each pair is randomly shown and participants are prompted to name the matching second word (BASELINE). After the last intervention night a different list of 30 word pairs is used for another session of encoding and retrieval (ASSESSMENT OF CHANGE)	The change in new learning performance will be assessed between the baseline measurement (morning before the first intervention night) and on the morning of the last intervention night (1.5 hour after waking), 3 days after.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvements in sleep physiology	EEG-data: Quality of slow wave sleep, number of slow oscillations, number of sleep spindles can all be measured by the data provided by the electroencephalographic recordings. A high densitiy electrode cap with 128 channels is used for this purpose.	Three consecutive nights of EEG measurement/polysomnography
Improvement in episodic memory performance at follow-ups	Face-occupation associative memory task	One week as well as 3 months after intervention
Improvement in new learning of episodic memory at follow-ups	Verbal associative memory task	One week as well as 3 months after intervention
Decreases in plasma amyloid-beta		Blood samples will be taken twice: on the morning before the first intervention night, on the morning after the last intervention night (3 days apart)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
General cognitive functions: working memory	A computer based visual n-back task is performed (established task for working memory)	Assessed four times: on the morning before the first intervention night, on the morning after the last intervention night, one week after and 3 months after the intervention
General cognitive functions: cognitive flexibility	A computer based task switch task is performed (established task for cognitive flexibility)	Assessed four times: on the morning before the first intervention night, on the morning after the last intervention night, one week after and 3 months after the intervention
General cognitive functions: cognitive inhibition	A computer based go/no go task is performed (established task for cognitive inhibition)	Assessed four times: on the morning before the first intervention night, on the morning after the last intervention night, one week after and 3 months after the intervention

Collaborators and Investigators

• Sponsor: University of Bern
• Investigators: Principal Investigator: Stefan Klöppel, Prof., University Hospital of Old Age Psychiatry and Psychotherapy

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2019
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: February 17, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: 2018-01979

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No