Acoustic Stimulation During Sleep: Effects on Memory and p-tau217 in MCI

NCT07529015 | Not Yet Recruiting

• 1 other identifier: PI25/01702
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

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:

• 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

Conditions

Alzheimer's Disease (AD); Mild Cognitive Impairment (MCI) Amnestic; Cognitively Unimpaired

Keywords

Alzheimer's disease; acoustic stimulation; declarative memory; amnestic mild cognitive impairment; sleep spindle; episodic memory; sleep EEG; slow-wave sleep; p-tau217; slow oscillation

Outcome Measures

Primary Outcomes (10)

• Impact on SWS: SO and sleep spindle density

  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.

  14 nights

• Impact on SWS: SO and sleep spindle duration

  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.

  14 nights

• Impact on SWS: SO and sleep spindle peak-to-peak amplitude

  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.

  14 nights

• Impact on SWS: SO and sleep spindle peak power frequency

  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.

  14 nights

• Impact on SWS: SO and sleep spindle power

  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.

  14 nights

• Impact on declarative memory consolidation: correct performance in the Verbal Paired Associates test

  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.

  Up to 3 months after intervention

• Impact on procedural memory consolidation: correct performance in the Motor Sequence Typing task

  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.

  Up to 3 months after intervention

• Impact on procedural memory consolidation: incorrect performance in the Motor Sequence Typing task

  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.

  Up to 3 months after intervention

• Impact on procedural memory consolidation: total attempt performance in the Motor Sequence Typing task

  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.

  Up to 3 months after intervention

• Impact on p-tau217

  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.

  Up to 3 months after intervention

Secondary Outcomes (1)

• Effect on GFAP and NfL

  Up to 3 months after intervention

Study Arms (2)

Real-PLAS

EXPERIMENTAL

Receiving phase-locked acoustic stimulation as an intervention

Device: Plase-Locked Acoustic Stimulation during slow-wave sleep

Sham-PLAS

SHAM COMPARATOR

Will have the same montage as real-PLAS, but no stimulation will be produced

Device: Phase-locked acoustic stimulation-Sham condition

Interventions

Phase-locked acoustic stimulation-Sham condition DEVICE

Participants will have the same setup as in the real-PLAS arm, wearing a mobile, wearable EEG device during sleep. Sleep will be recorded using EEG, and an algorithm will detect slow oscillations (SOs; \>1 Hz). No acoustic stimulation will be applied in the sham-PLAS arm.

Sham-PLAS

Plase-Locked Acoustic Stimulation during slow-wave sleep DEVICE

Participants will wear a mobile, wearable EEG device during sleep. Sleep will be recorded using EEG, and an algorithm will detect slow oscillations (SOs; \>1 Hz). In the real-PLAS arm, acoustic stimulation will be applied in phase with the up-state of these slow oscillations. Specifically, the algorithm will detect each SO and trigger brief pink-noise bursts synchronized with the up-state phase, ensuring phase-locked acoustic stimulation (PLAS) is delivered precisely to enhance slow-wave activity.

Also known as: Closed-loop acoustic stimulation, Closed-loop auditive stimulation

Real-PLAS

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of aMCI according to the NIA-AA criteria (Albert et al., 2011) and positive state of plasma p-tau217.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recerca Biomèdica de Lleida-Fundació Dr. Pifarré (IRBLleida): lead

Study Sites (1)

Hospital Universitari Santa Maria de Lleida

Lleida, Catalonia, 25198, Spain

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Central Study Contacts

Farida Dakterzada, PhD

CONTACT

+34-973702413; farida.dakterzada@udl.cat

Gerard Piñol-Ripoll, MD, PhD

CONTACT

gerard_437302@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: April 14, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

ES (1)