Sleep Stimulation to Enhance Waste Clearance in the Brain

N/ANot Yet RecruitingNCT07051239

Erasme University Hospital105 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

105

Conditions

Healthy Subjective Cognitive Decline (SCD)Mild Cognitive Impairment (MCI)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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: * Proficiency in the French language (close to native level) to complete the neuropsychological evaluation and cognitive tests. * MRI compatibility: absence of metallic materials in the body (implants, vascular clips, certain types of orthopedic material, etc.), a pacemaker or other types of stimulators, cochlear implants, or any other electronic devices. Exclusion criteria: * Current or past psychiatric or neurological conditions (except for those directly associated with the patient group). * The presence of severe untreated sleep disorders. * The presence of irregular sleep-wake cycles (due to shiftwork or extreme chronotype). * The presence of moderate depression or high levels of anxiety. * Ongoing treatment with psychotropic medications (benzodiazepines, antidepressants). * Regular or excessive consumption of alcohol or caffeinated drinks. * Consumption of other psychoactive substances known to have an impact on the central nervous system. * Insufficient visual or auditory acuity to complete the assessments if uncorrected. Normal hearing is required for sound stimulation to be effective. * Claustrophobia that prevents undergoing brain imaging (MRI). * Pregnancy or currently breastfeeding

Outcomes

Primary Outcomes

Plasma biomarkers

Levels of plasma biomarkers associated with neurodegeneration and brain health will be compared between stimulation and sham interventions.

Time frame: Blood samples will be collected the morning after each intervention phase. Interventions are separated by one week.

Secondary Outcomes

Glymphatic function

Magnetic resonance imaging (MRI) derived measures will serve as proxies for glymphatic function and will be compared between stimulation and sham interventions.

Time frame: MRI scans will be performed the morning after each intervention phase. Interventions are separated by one week.

CLAS evoked responses

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.

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: After each intervention phase. Interventions are separated by one week.

Alertness and sustained attention

Performance (reaction times, lapses) in the psychomotor vigilance task (PVT).

Time frame: 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.

Time frame: 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.

Time frame: MRI scans will be performed the morning after each intervention phase. Interventions are separated by one week.

Sleep Stimulation to Enhance Waste Clearance in the Brain

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts