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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy intervention | Experimental | Acoustic stimulation |
|
| Healthy sham | Sham Comparator | No stimulation |
|
| At risk intervention | Experimental | Acoustic stimulation |
|
| At risk sham | Sham Comparator | No stimulation |
|
| MCI (mild cognitive impairment) intervention | Experimental | Acoustic stimulation |
|
| MCI (mild cognitive impairment) sham | Sham Comparator | No stimulation |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Closed loop acoustic stimulation | Other | 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 |
| 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. |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stefan Klöppel, Prof. | University hospital of old age psychiatry and psychotherapy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of Old Age Psychiatry and Psychotherapy | Bern | 3000 60 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38744792 | Derived | 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. |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
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| Sham acoustic stimulation | Other | 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. |
|
| 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) |
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 |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |