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

Randomized, Double-Blind, Placebo-Controlled Investigation to Validate the Efficacy and Safety of an Auditory Stimulation Treatment During Sleep to Improve Cognitive Abilities Related to Long-Term Memory in Amnestic Mild Cognitive Impairment (aMCI)

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.

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)