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

Official title

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

Overview

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

Interventions

• 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 activit
• 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.

Primary outcome measures

• Impact on SWS: SO and sleep spindle density [Time frame: 14 nights]
• Impact on SWS: SO and sleep spindle duration [Time frame: 14 nights]
• Impact on SWS: SO and sleep spindle peak-to-peak amplitude [Time frame: 14 nights]
• Impact on SWS: SO and sleep spindle peak power frequency [Time frame: 14 nights]
• Impact on SWS: SO and sleep spindle power [Time frame: 14 nights]
• Impact on declarative memory consolidation: correct performance in the Verbal Paired Associates test [Time frame: Up to 3 months after intervention]
• Impact on procedural memory consolidation: correct performance in the Motor Sequence Typing task [Time frame: Up to 3 months after intervention]
• Impact on procedural memory consolidation: incorrect performance in the Motor Sequence Typing task [Time frame: Up to 3 months after intervention]
• Impact on procedural memory consolidation: total attempt performance in the Motor Sequence Typing task [Time frame: Up to 3 months after intervention]
• Impact on p-tau217 [Time frame: Up to 3 months after intervention]

Secondary outcome measures (1)

• Effect on GFAP and NfL [Time frame: Up to 3 months after intervention]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Other

Study locations

Spain · 1 center

• Hospital Universitari Santa Maria de Lleida — Lleida

Identifiers

NCT: NCT07529015 · PI25/01702

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗