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

Prior treatment

• 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.

Other illness

• 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.
• Epilepsy with active treatment within the last 5 years, or any neurological comorbidity that may cause cognitive impairment or structural brain damage.

Other

• Alcohol or psychotropic substance abuse.
• 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.

• 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.