Alzheimer's Disease (AD), Cognitively Unimpaired, Mild Cognitive Impairment (MCI) Amnestic
Conditions
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
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: 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
DEVICEPlase-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.
DEVICEPhase-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.
Sponsors
Institut de Recerca Biomèdica de Lleida-Fundació Dr. Pifarré (IRBLleida)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact on SWS: SO and sleep spindle density | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Effect on GFAP and NfL | Up to 3 months after intervention | 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. |
Countries
Spain
Contacts
CONTACTFarida Dakterzada, PhD
CONTACTGerard Piñol-Ripoll, MD, PhD
Outcome results
None listed