Overview

This summary focuses on the acoustic stimulation part of the study.

The goal of this interventional study is to learn if acoustic stimulation during sleep works to improve cognitive function in patients with Alzheimer's disease. It will also learn about safety and feasibility. The main questions are:

Does acoustic stimulation during NREM sleep improve cognitive function in patients with mild cognitive impairment due to Alzheimer's disease (AD-MCI)? How does acoustic stimulation compare with sham stimulation?

Researchers will compare acoustic stimulation with sham stimulation. Participants will:

Be assigned to the acoustic stimulation group (n=20) or the sham stimulation group (n=20).

Receive a familiar, comfortable sound at the bedside during stable NREM sleep, or sham stimulation, with 30 seconds of stimulation every 1 minute, triggered upon entering NREM sleep, with no limit on the number of stimulations.

Complete cognitive assessments and sleep EEG monitoring before and after the intervention.

Be monitored for safety throughout the study. The study is sponsored by Xuanwu Hospital, Capital Medical University. It is funded by the National Natural Science Foundation of China Key International Cooperation Project (Grant No. 82220108009). The study period runs from ethics approval to December 2024. No other centers are participating. Participants will be 60-75 years old and recruited from the neurology wards of Xuanwu Hospital.

Eligibility

Inclusion Criteria:

\- (1) Meets the diagnostic criteria for mild cognitive impairment (according to Petersen criteria): ① insidious onset; ② memory impairment is the primary complaint; ③ objective evidence of memory decline (defined quantitatively as a decline of more than 1.5 standard deviations below age- and education-matched controls); ④ may be accompanied by other cognitive impairments, but memory decline is more prominent; ⑤ general cognitive function is normal; ⑥ preservation of activities of daily living, with an Activities of Daily Living (ADL) scale score \<23; ⑦ does not meet the diagnostic criteria for dementia; ⑧ imaging findings support the diagnosis.

(2) Amyloid PET positivity or reduced cerebrospinal fluid amyloid levels. (3) The patient should have a stable and reliable caregiver, or at least be able to maintain frequent contact with a caregiver. The caregiver must be able to accompany and assist the patient throughout the entire study, must accompany the subject to study visits, and must have sufficient interaction and communication with the subject to provide valuable information for the scoring of various scales.

Exclusion Criteria:

• (1) Presence of memory and cognitive decline caused by other non-AD conditions, such as other types of dementia, including but not limited to mixed dementia (AD-VaD), vascular dementia (VD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), Huntington's disease-related dementia, and frontotemporal dementia (FTD); endocrine disorders (e.g., thyroid disease, parathyroid disease); folate or vitamin B12 deficiency; or dementia caused by any other reason.

  (2) At screening, MRI shows significant focal lesions: more than 2 infarcts with a diameter greater than 2 cm, or infarcts in key regions such as the thalamus, hippocampus, entorhinal cortex, perirhinal cortex, angular gyrus, and other cortical and subcortical gray matter nuclei.

  (3) Presence of moderate to severe white matter degeneration (Fazekas score 3-6).

  (4) Presence of metallic foreign bodies or other implanted electronic devices, or claustrophobia, etc., which preclude TMS treatment or MRI scanning.

  (5) Severe visual, auditory, motor, or consciousness impairment that prevents cooperation with examinations and treatment.

  (6) History of seizures (presence of at least 2 unprovoked seizures occurring more than 24 hours apart, or diagnosis of an epilepsy syndrome, or a seizure within the past 12 months).

  (7) Acute cardiovascular or cerebrovascular events (e.g., unstable angina, severe arrhythmia, myocardial infarction, transient ischemic attack, or ischemic stroke) within 3 months before screening.

  (8) Severe systemic diseases involving the heart, lungs, liver, kidneys, etc., identified by laboratory tests or examinations, and not controlled by conventional medication.

  (9) Patients with concurrent malignant tumors; or patients with a life expectancy of less than 1 year due to causes other than AD.

  (10) History of alcohol or drug abuse. (11) Received other TMS treatment within 3 months. (12) Participated in or is currently participating in another clinical trial within 3 months.