Development of a Novel Multidimensional Therapeutic Intervention Protocol for MCI

Summary

As populations age, Alzheimer's disease (AD) is increasing while disease-modifying drugs remain elusive, making early diagnosis and intervention essential. Building on advances in neuromodulation and virtual reality (VR), we target amnestic mild cognitive impairment (aMCI)-the prodromal stage of AD-as a key window for prevention. Preliminary evidence shows disrupted theta-delta phase-amplitude coupling in prefrontal and temporal cortices in aMCI, whereas olfactory enrichment can enhance hippocampal synaptic function, improve cognition, and potentially lower AD risk. We will conduct a large-scale clinical cohort study to test the neural mechanisms and clinical efficacy of multi-site, cross-frequency transcranial alternating current stimulation (tACS) combined with multisensory (visual-olfactory-auditory) VR. A comprehensive database spanning demographic, neuropsychological, biochemical, neuroimaging, and neuromodulation parameters will guide optimal protocols and provide objective evidence for non-pharmacological interventions, informing development of a microcurrent brain stimulator and a portable VR device.

Conditions

• MCI-AD, Early Stage Alzheimer's Disease

Interventions

BEHAVIORAL

Olfactory stimulation

Olfactory stimulation were set as follows: Essential oil types: yuzu, lavender, lemon, and mint. Concentration: 158 μL of essential oil + 50 mL of water. The mixed solution was poured into the test tubes of the olfactory instrument, ensuring that the liquid levels of the four solutions were kept at the same height. Each scent was released for 30 seconds, followed by a 10-second air interval, with each cycle lasting 20 minutes.

BIOLOGICAL

Temporal Interference,TI

During stimulation, the parameters were set as follows: Δf=40Hz (2000Hz vs. 2040Hz) 2mA Stimulation duration: 20min We fixed the stimulation protocol and used a standard head to simulate stimulation of the entorhinal region.

COMBINATION_PRODUCT

Olfactory-TI Stimulation

During stimulation, the parameters were set as follows: Δf=40Hz (2000Hz vs. 2040Hz) 2mA Stimulation duration: 20min We fixed the stimulation protocol and used a standard head to simulate stimulation of the entorhinal region. Olfactory stimulation were set as follows: Essential oil types: yuzu, lavender, lemon, and mint. Concentration: 158 μL of essential oil + 50 mL of water. The mixed solution was poured into the test tubes of the olfactory instrument, ensuring that the liquid levels of the four solutions were kept at the same height. Each scent was released for 30 seconds, followed by a 10-second air interval, with each cycle lasting 20 minutes.

COMBINATION_PRODUCT

Sham Control

During stimulation, the parameters were set as follows: Δf=0Hz (2000Hz vs. 2000Hz) 2mA Stimulation duration: 20min. Olfactory stimulation were set as follows: Essential oil types: air. lasting 20 minutes.

Sponsors & Collaborators

• Shanghai Mental Health Center

  collaborator OTHER

• Yuan Shen

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-10-01

Primary Completion

2026-11-01

Completion

2026-12-01