Auditory Stimulation During Sleep to Enhance Long-Term Memory in Amnestic MCI

Bitbrain37 enrolled

Overview

This study aims to evaluate the efficacy and safety of Elevvo AudiStim, a sleep auditory stimulation device, as a symptomatic treatment for patients with amnestic mild cognitive impairment (aMCI).

Amnestic Mild Cognitive Impairment (aMCI) is a precursor of dementia that involves memory impairment as a primary symptom. The condition presents a valuable opportunity for intervention before a potential progression to more severe, life-altering stages. A technique called "auditory stimulation during sleep" has previously been shown to improve memory by triggering neural oscillations such as slow waves and sleep spindles, which are implicated in memory processing. We hypothesize that the technique might improve memory also in patients with aMCI. This investigation is thus designed to systematically assess both the product's efficacy as a symptomatic treatment for patients with amnestic mild cognitive impairment (aMCI) and its overall safety profile. After an initial calibration night ("Night 0"), two experimental nights will be performed ("Night 1" and "Night 2"), separated by 14 days. 7 days after each experimental night, a daytime long-term follow-up will be performed ("LT1" and "LT2"). Participants will receive either real or sham auditory stimulation during sleep, such that all participants will participate in both these conditions in a randomized balanced order.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Mild Cognitive Impairment (MCI)Amnestic Mild Cognitive Impairment - aMCI Alzheimer or Mild Cognitive Impairment

Interventions

Auditory StimulationPROCEDURE

Brief auditory stimuli (50-ms bursts of pink noise) are delivered to patients once they have entered stable non-rapid eye movement (NonREM) sleep. The volume is automatically adjusted to optimize the induction of targeted neural oscillations, specifically slow waves and sleep spindles, while minimizing the risk of arousal.

Placebo stimulationPROCEDURE

All procedures are identical to the Auditory stimulation condition but the tone volume is set to 0.

Eligibility

Sex: ALLMin age: 50 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age range \> 50 years and ≤ 75 years * Native Spanish speaker * Normal or corrected-to-normal color vision * Diagnosis of Alzheimer's disease with an amnestic phenotype at the mild cognitive impairment stage, confirmed according to the current clinical criteria of NIA-AA (2024) and IWG (2024), as well as the clinical protocols of the treating hospital * Sufficient hearing without the use of a hearing aid (participant with a hearing threshold of 50 dB or higher in the calibration night hearing test will be excluded) Exclusion Criteria: * Patients with severe and/or complex chronic systemic diseases: Advanced heart disease, Advanced chronic kidney disease, for example, stage 4 or 5, Severe lung disease, such as GOLD stage III-IV COPD, Metastatic or end-stage cancer, Severe hematologic disorders, Active or chronic uncontrolled infectious diseases (e.g., untreated HIV) * Evidence of strategic infarcts or other findings on neuroimaging that could be the cause of secondary cognitive impairment * Abuse of alcohol or other psychotropic substances * Diagnosed for depression or any severe psychiatric disorder in the 5 years prior to the evaluation * Changes in treatment with benzodiazepines or antidepressants in the 6 months prior to the initial evaluation * Treatment with neuroleptics * Epilepsy with active treatment (within the last 5 years) or any comorbidity with a neurological disease that may cause cognitive impairment or brain damage * Illiteracy * Moderate or severe sleep apnea (without CPAP during the study)

Locations (1)

Bit&Brain Technologies SL

Zaragoza, Zaragoza, Spain

Outcomes

Primary Outcomes

Performance (pre vs post-sleep) in a word pair association task

Memory performance in this task is measured as the number of word pairs recalled during morning and long-term recall, subtracted from the number of word pairs indicated during immediate recall. This metric will be compared between the two experimental conditions.

Time frame: Immediate recall: right before Nights 1/2 (1 hour before going to sleep); Morning recall: right after Nights 1/2 (1 hour after waking up); Long-term recall: during LT 1/2 (7 days after the start day of Nights 1/2).

Performance (pre vs post-sleep) in a visuospatial memory task

Memory performance is measured as the number of recognized images and correctly indicated image locations during morning and long-term recall, subtracted from the respective numbers during immediate recall. This metric will be compared between the two experimental conditions.

Secondary Outcomes

Working memory performance

Working memory performance will be measured by the number of correct responses in the Sternberg task, administered after sleep in both conditions. This metric will be compared between conditions to evaluate the effect of the intervention.

Time frame: Morning recall: right after Nights 1/2 (1 hour after waking up); Long-term recall: during LT 1/2 (7 days after the start day of Nights 1/2).

Slow wave and sleep spindle activity

Neural oscillations will be analyzed using event detection to estimate event rates (incidences per minute) and event amplitudes (uV), as well as spectral analysis to quantify power (uV2/Hz) across relevant frequencies. The results will be evaluated by calculating linear correlations between these metrics (sleep spindle rate, amplitude, power, as well as slow-wave rate, amplitude, and power) and the two primary endpoints.

Data from ClinicalTrials.gov

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