The Impact of Phase-locked Acoustic Stimulation on Sleep Structure, Memory Consolidation, and Plasma p-tau217 in Patients With Mild Cognitive Impairment
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 114
- Locations
- 1
- Primary Endpoint
- Impact on SWS: SO and sleep spindle density
Study Overview
Brief Summary
The goal of this clinical trial is to determine whether acoustic stimulation during sleep can enhance slow-wave sleep (SWS), improve cognitive function, and reduce AD-related pathology in individuals with mild cognitive impairment (MCI), compared with cognitively healthy participants.
The main questions it aims to answer are:
- Does acoustic stimulation increase SWS (e.g., slow oscillation and sleep spindle activity) in individuals with MCI?
- Does enhancing SWS lead to improvements in memory and cognitive performance?
- Does acoustic stimulation influence plasma p-tau217 levels as a marker of underlying Alzheimer's disease pathology? Researchers will compare participants receiving acoustic stimulation during sleep with those not receiving stimulation to evaluate its effects on sleep architecture, cognition, and plasma biomarkers.
Participants will:
- Undergo sleep recordings to assess sleep architecture, including SWS, slow oscillations, and sleep spindles
- Receive acoustic stimulation during sleep across multiple nights
- Complete cognitive assessments, particularly memory-related tasks
- Provide blood samples to measure plasma p-tau217 levels
- Provide clinical and demographic information for analysis
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 60 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Diagnosis of aMCI according to the NIA-AA criteria (Albert et al., 2011) and positive state of plasma p-tau
- •Diagnosis of aMCI according to the NIA-AA criteria (Albert et al., 2011) and negative state of plasma p-tau217 for aMCI negative group.
- •Cognitively unimpaired older subjects aged ≥ 65 years, Mini-mental state examination ≥28, and negative for plasma p-tau217.
Exclusion Criteria
- •Diagnosis of dementia due to AD or any other type of dementia.
- •Presence of any diagnosed sleep disorder such as narcolepsy, severe insomnia, severe obstructive sleep apnea, or severe chronic lack of sleep.
- •Hearing problems.
- •Analphabet individuals.
- •Comorbidities such as cancer, severe depression, severe renal or hepatic insufficiency, history of seizures, and severe cardiac or respiratory failure.
- •Alcohol and substance abuse.
- •Magnetic resonance imaging (MRI) evidence of stroke, hydrocephalus, a space-occupying lesion, or any clinically relevant central nervous system disease.
- •Existence of untreated (or treated for less than 3 months prior to the screening visit) vitamin B12 or folate deficiency.
- •Presence of untreated thyroid disease.
- •Use of betablockers, antidepressants, neuroleptics, and hypnotics, within 15 days before conducting polysomnography.
Arms & Interventions
Real-PLAS
Receiving phase-locked acoustic stimulation as an intervention
Intervention: Plase-Locked Acoustic Stimulation during slow-wave sleep (Device)
Sham-PLAS
Will have the same montage as real-PLAS, but no stimulation will be produced
Intervention: Phase-locked acoustic stimulation-Sham condition (Device)
Outcomes
Primary Outcomes
Impact on SWS: SO and sleep spindle density
Time Frame: 14 nights
Two defining features of slow-wave sleep (SWS) are slow oscillations (SO) and sleep spindles. Accordingly, the impact of multi-night PLAS on SWS in the study population will be evaluated by measuring the density of both features (expressed as counts per 30 seconds). Post-intervention measurements, including follow-up assessments, will be compared with the baseline night, during which no stimulation is applied, and with the sham group.
Impact on SWS: SO and sleep spindle duration
Time Frame: 14 nights
Two defining features of slow-wave sleep (SWS) are slow oscillations (SO) and sleep spindles. Accordingly, the impact of multi-night PLAS on SWS in the study population will be evaluated by measuring the duration of both features (expressed in seconds). Post-intervention measurements, including follow-up assessments, will be compared with the baseline night, during which no stimulation is applied, and with the sham group.
Impact on SWS: SO and sleep spindle peak-to-peak amplitude
Time Frame: 14 nights
Two defining features of slow-wave sleep (SWS) are slow oscillations (SO) and sleep spindles. Accordingly, the impact of multi-night PLAS on SWS in the study population will be evaluated by measuring the peak-to-peak amplitude of both features (expressed in µV).Post-intervention measurements, including follow-up assessments, will be compared with the baseline night, during which no stimulation is applied, and with the sham group.
Impact on SWS: SO and sleep spindle peak power frequency
Time Frame: 14 nights
Two defining features of slow-wave sleep (SWS) are slow oscillations (SO) and sleep spindles. Accordingly, the impact of multi-night PLAS on SWS in the study population will be evaluated by measuring the peak power frequency of each feature (expressed in Hz). Post-intervention measurements, including follow-up assessments, will be compared with the baseline night, during which no stimulation is applied, and with the sham group.
Impact on SWS: SO and sleep spindle power
Time Frame: 14 nights
Two defining features of slow-wave sleep (SWS) are slow oscillations (SO) and sleep spindles. Accordingly, the impact of multi-night PLAS on SWS in the study population will be evaluated by measuring the power of both features (expressed in µV2). Post-intervention measurements, including follow-up assessments, will be compared with the baseline night, during which no stimulation is applied, and with the sham group.
Impact on declarative memory consolidation: correct performance in the Verbal Paired Associates test
Time Frame: Up to 3 months after intervention
The impact of multi-night PLAS on declarative memory performance in the study population will be assessed using the Verbal Paired Associates (VPA) test. Performance will be quantified as the number of correctly recalled word pairs. Post-intervention measurements, including follow-up assessments, will be compared with the first recall, conducted in the morning after the baseline night, and with the sham group.
Impact on procedural memory consolidation: correct performance in the Motor Sequence Typing task
Time Frame: Up to 3 months after intervention
The impact of multi-night PLAS on procedural memory performance in the study population will be assessed using the Motor Sequence Typing task (MST). Performance will be quantified as the number of correctly executed sequences (i.e., keypresses) per trial. Post-intervention measurements, including follow-up assessments, will be compared with the first recall, conducted in the morning after the baseline night, and with the sham group.
Impact on procedural memory consolidation: incorrect performance in the Motor Sequence Typing task
Time Frame: Up to 3 months after intervention
The impact of multi-night PLAS on procedural memory performance in the study population will be assessed using the Motor Sequence Typing task (MST). Performance will be quantified as the number of incorrectly executed sequences (i.e., keypresses) per trial. Post-intervention measurements, including follow-up assessments, will be compared with the first recall, conducted in the morning after the baseline night, and with the sham group.
Impact on procedural memory consolidation: total attempt performance in the Motor Sequence Typing task
Time Frame: Up to 3 months after intervention
The impact of multi-night PLAS on procedural memory performance in the study population will be assessed using the Motor Sequence Typing Task (MST). Performance will be quantified as the total number of executed sequences (i.e., keypresses) per trial. Post-intervention measurements, including follow-up assessments, will be compared with the first recall, conducted in the morning after the baseline night, and with the sham group.
Impact on p-tau217
Time Frame: Up to 3 months after intervention
Post-intervention plasma levels of p-tau217(pg/mL), including follow-up assessments, will be measured in the study population and compared with baseline values as well as with the sham group.
Secondary Outcomes
- Effect on GFAP and NfL(Up to 3 months after intervention)
Investigators
Farida Dakterzada
Principal Investigator
Institut de Recerca Biomèdica de Lleida-Fundació Dr. Pifarré (IRBLleida)