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

The Impact of Phase-locked Acoustic Stimulation on Sleep Structure, Memory Consolidation, and Plasma p-tau217 in Patients With Mild Cognitive Impairment

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:

1. Does acoustic stimulation increase SWS (e.g., slow oscillation and sleep spindle activity) in individuals with MCI?
2. Does enhancing SWS lead to improvements in memory and cognitive performance?
3. 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 Overview

• Status: Not yet recruiting
• Conditions: Alzheimer's Disease (AD); Mild Cognitive Impairment (MCI) Amnestic; Cognitively Unimpaired
• Intervention / Treatment: Device: Plase-Locked Acoustic Stimulation during slow-wave sleep; Device: Phase-locked acoustic stimulation-Sham condition

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Farida Dakterzada, PhD; Phone Number: +34-973702413; Email: farida.dakterzada@udl.cat
• Study Contact Backup: Name: Gerard Piñol-Ripoll, MD, PhD; Email: gerard_437302@hotmail.com

Study Locations

• Spain
  • Catalonia
    • Lleida, Catalonia, Spain, 25198
      • Hospital Universitari Santa Maria de Lleida
      • Contact: Cristina Balaguer; Phone Number: 173 +34-937727222; Email: cbalaguer@irblleida.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Real-PLAS; Receiving phase-locked acoustic stimulation as an intervention	Device: Plase-Locked Acoustic Stimulation during slow-wave sleep; 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.; Other Names: Closed-loop acoustic stimulation; Closed-loop auditive stimulation
Sham Comparator: Sham-PLAS; Will have the same montage as real-PLAS, but no stimulation will be produced	Device: Phase-locked acoustic stimulation-Sham condition; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on GFAP and NfL	Post-intervention plasma levels of Glial fibrillary acidic protein (GFAP, pg/mL) and neurofilament light (NfL, 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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 18, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's disease; episodic memory; amnestic mild cognitive impairment; acoustic stimulation; slow-wave sleep; p-tau217; declarative memory; sleep spindle; sleep EEG; slow oscillation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease
• Other Study ID Numbers: PI25/01702

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No