Home-Based Closed-Loop Auditory Stimulation to Enhance Slow-Wave Activity in MCI Due to Alzheimer's Disease: A Proof-of-Concept Study

Summary

This proof-of-concept study explores whether long-term home-based closed-loop auditory stimulation during sleep enhances slow-wave activity (SWA) and yields preliminary efficacy signals in patients with amnestic mild cognitive impairment due to Alzheimer's disease (MCI-AD), confirmed by cerebrospinal fluid (CSF) biomarkers or positron emission tomography (PET). The intervention is self-administered at participants' homes over an initial treatment period of 3 months, followed by a 1-month off-treatment (washout) period. Participants may then enter an optional extension phase consisting of 3 additional months of treatment followed by a second 1-month washout period, for a total study duration of up to 8 months. Participants who complete the Nana-Lab Study (NCT07402590) may be invited to provide informed consent for screening and potential enrollment in this study. All enrolled participants receive nightly active treatment during intervention periods. This study does not include randomization or a sham control group.

Interventions

• Closed-Loop Auditory Stimulation · DEVICE

  The system delivers brief auditory stimuli (pink noise bursts) that are time-locked to the up-phase of endogenous slow oscillations during non-rapid eye movement (NREM) sleep, as detected in real time using electroencephalography (EEG). Stimulation is withheld in approximately half of detected slow oscillations (Sham) to serve as a within-session control condition for the acute effects of stimulation. The other half of the slow oscillations are stimulated at a volume between 30-60 dB (Stim), which is personalized to the patient and adapts during the night to improve response while reducing awakenings. The objective of the stimulation is to enhance slow-wave activity (SWA) during deep sleep through phase-specific entrainment of endogenous slow-wave activity. The intervention is self-administered using a portable system adapted for use in patients with MCI. Participants are instructed to use the device for as many nights as possible throughout the study period.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion criteria:

* Age between 50 and 75 years (inclusive).
* Spanish as native language.
* Diagnosis of amnestic mild cognitive impairment due to Alzheimer's disease, confirmed by cerebrospinal fluid biomarkers or amyloid PET.
* Normal or corrected-to-normal color vision (required for completion of visual-analog study assessments).
* Adequate hearing to perceive the auditory stimuli used in the intervention, defined as a hearing threshold of 50 dB or below, assessed during the screening session.

Exclusion criteria:

* Severe systemic or complex chronic disease that, in the investigator's judgment, would compromise participant safety or data quality, including but not limited to: advanced heart disease; advanced chronic kidney disease (stage 4 or 5); severe pulmonary disease (e.g., COPD GOLD stage III-IV); metastatic or terminal cancer; severe hematological disorders; or active or uncontrolled chronic infectious disease (e.g., untreated HIV).
* Evidence on neuroimaging of strategic infarcts or other findings that may account for secondary cognitive impairment.
* Alcohol or psychotropic substance abuse.
* Diagnosis of depression or any severe psychiatric disorder within the 5 years prior to evaluation.
* Changes in benzodiazepine or antidepressant treatment within the 6 months prior to baseline evaluation.
* Current treatment with neuroleptics.
* Epilepsy with active treatment within the last 5 years, or any neurological comorbidity that may cause cognitive impairment or structural brain damage.
* Unable to read and write in Spanish.
* Inability to use the study device effectively, as determined during the screening session. This includes, but is not limited to, anatomical or dermatological factors preventing adequate electrode placement, or excessive EEG signal artifacts that prevent reliable detection of sleep oscillations.

Sites (1)

• Bit&Brain Technologies SL, Zaragoza, Zaragoza, Spain