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| Name | Class |
|---|---|
| University of Amsterdam | OTHER |
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This study aims to examine whether multi-night closed-loop auditory stimulation (CLAS) during sleep can enhance waste clearance and memory consolidation in healthy adults and older adults with subjective cognitive decline or mild cognitive impairment who exhibit elevated brain amyloid levels identified through prior clinical screening. Specifically, the study investigates whether sleep stimulation increases the clearance of plasma biomarkers related to neurodegeneration, improves the brain's waste clearance system, and supports memory consolidation. Participants will undergo five nights each of CLAS and sham (no stimulation) interventions, with a washout period in between. They will also complete clinical assessments, including MRI scans, blood sample collection, and cognitive testing, and will keep track of subjective sleep quality, sleepiness, mood, and fatigue throughout the interventions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy young, auditory stimulation, then sham | Experimental |
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| Healthy young, sham, then auditory stimulation | Experimental |
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| Healthy old, auditory stimulation, then sham | Experimental |
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| Healthy old, sham then auditory stimulation | Experimental |
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| Positive amyloid load group, auditory stimulation, then sham | Experimental |
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| Positive amyloid load group, sham, then auditory stimulation | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Closed-loop acoustic stimulation | Other | At-home sleep will be monitored using an EEG headband. Non-awakening auditory stimuli will be delivered during non-rapid eye movement sleep (NREM), timed to the ascending phase of slow waves, using either active or control (sham) conditions. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma biomarkers | Levels of plasma biomarkers associated with neurodegeneration and brain health will be compared between stimulation and sham interventions. | Blood samples will be collected the morning after each intervention phase. Interventions are separated by one week. |
| Measure | Description | Time Frame |
|---|---|---|
| Glymphatic function | Magnetic resonance imaging (MRI) derived measures will serve as proxies for glymphatic function and will be compared between stimulation and sham interventions. | MRI scans will be performed the morning after each intervention phase. Interventions are separated by one week. |
| CLAS evoked responses |
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For the positive amyloid load group:
-Participants who meet the criteria of subjective cognitive decline or mild cognitive impairment (Clinical Dementia Rating < 2; Mini-Mental State Examination ≥ 21) and brain amyloid-beta (Aβ) accumulation confirmed by CSF or amyloid-PET, the inclusion age range is 55-80 years.
For healthy groups:
-Inclusion age range is 18-80 years.
Inclusion criteria:
Exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mélanie Strauss, MD, PhD | Contact | +32 2 555 55 39 | melanie.strauss@hubruxelles.be | |
| Rebeca Sifuentes Ortega, PhD | Contact | rebeca.sifuentes.ortega@ulb.be |
| Name | Affiliation | Role |
|---|---|---|
| Mélanie Strauss, MD, PhD | Université Libre de Bruxelles | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Universitaire de Bruxelles | Brussels | Belgium |
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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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EEG responses locked to the acoustic stimulation will be examined (phase, amplitude, power, slow oscillations, spindle coupling) during stimulation and sham night recordings. Associations between APOE phenotype, age, amyloid accumulation, brain structure and function, baseline memory performance, sleep quality and responses to CLAS will be evaluated. |
| Each night of sleep during each intervention phase, whether receiving stimulation or sham. |
| Slow wave activity (SWA) | EEG SWA will be assessed during NREM sleep periods from each intervention (stimulation and sham) | Each night of sleep during each intervention phase, whether receiving stimulation or sham. |
| Sleep architecture | As measured with the EEG headband, macro- (e.g., duration, latency, distribution of sleep stages), and micro-architecture (slow waves, sleep spindles, rapid eye movements, arousals) differences between stimulation and sham conditions will be assessed. | Each night of sleep during each intervention phase, whether receiving stimulation or sham. |
| Change in memory performance | Performance change in declarative memory tasks (cued-recall and recognition measures) will be evaluated. | Before and after each intervention period. Interventions are separated by one week. |
| Encoding capacity | Performance in a continuous mnemonic discrimination task (recognition and mnemonic discrimination measures) will be assessed after both stimulation and sham interventions. | After each intervention phase. Interventions are separated by one week. |
| Alertness and sustained attention | Performance (reaction times, lapses) in the psychomotor vigilance task (PVT). | The PVT task will be assessed before and after each intervention phase. Interventions are separated by one week. |
| Subjective measures after sleep | As measured with morning questionnaires, subjective sleep quality, fatigue, sleepiness, mood, and affect, will be assessed every morning during each stimulation and sham intervention. | Each morning throughout the intervention phase. |
| Resting-state functional connectivity | Changes in resting-state functional connectivity measured with fMRI will be compared between stimulation and sham interventions. | MRI scans will be performed the morning after each intervention phase. Interventions are separated by one week. |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |