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Development of a Novel Multidimensional Therapeutic Intervention Protocol for MCI

Y

Yuan Shen

Status

Not yet enrolling

Conditions

MCI-AD, Early Stage Alzheimer's Disease

Treatments

Combination Product: Olfactory-TI Stimulation
Biological: Temporal Interference,TI
Combination Product: Sham Control
Behavioral: Olfactory stimulation

Study type

Interventional

Funder types

Other

Identifiers

NCT07196592
B20250001I

Details and patient eligibility

About

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.

Full description

With the accelerating pace of population aging, the prevalence of Alzheimer's disease (AD) continues to rise, yet effective disease-modifying pharmacotherapies remain unavailable. Early diagnosis and intervention are critical to slowing cognitive decline and reducing disease burden. In recent years, rapid advances in neuromodulation and virtual reality (VR) have opened new avenues for mechanistic studies and functional brain rehabilitation in AD and other neurodegenerative disorders. Amnestic mild cognitive impairment (aMCI) is widely regarded as the prodromal stage of AD and represents a key window for prevention and treatment. Developing innovative non-pharmacological therapies for individuals at this early stage has therefore become an urgent clinical priority. Preliminary studies indicate that people with aMCI exhibit a significant loss of phase-amplitude coupling (PAC) between theta and delta rhythms in the prefrontal cortex and temporal lobe, whereas olfactory-enriched environmental stimulation can enhance hippocampal synaptic function, improve cognition, and lower AD risk. Accordingly, we propose a large-scale clinical cohort study to investigate the neural-circuit mechanisms and clinical efficacy of multi-site, cross-frequency transcranial alternating current stimulation (tACS) and multisensory VR integrating visual, olfactory, and auditory inputs for the treatment of aMCI. We will establish a comprehensive database encompassing demographic, neuropsychological, biochemical, neuroimaging, and neuromodulation parameters. Ultimately, this work will provide optimal theoretical parameters and objective evidence to guide the development of non-pharmacological interventions for AD-specifically, a microcurrent brain stimulator and a portable VR device.

Enrollment

300 estimated patients

Sex

All

Ages

60+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Baseline screening inclusion criteria: a) Age ≤ 65 years and ≤ 85 years; b) Education duration ≥ 1 year; c) Normal cognitive function at enrollment: MMSE total score: non-illiterate (primary school or below) ≥ 20 points, primary school or above ≥ 24 points; d) Corrected vision and hearing are basically normal, and able to complete cognitive assessment.

Exclusion criteria

Baseline screening exclusion criteria: a) Neurological/psychiatric disorders affecting cognitive function: depression, schizophrenia, mental retardation, Parkinson's disease, etc.; b) Severe physical illnesses: cardiovascular disease, cerebrovascular disease, tumors, diabetes, kidney disease, and hypertension stage III or above; c) Autoimmune inflammatory diseases such as rheumatoid arthritis, lupus erythematosus, osteoarthritis, and multiple sclerosis.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

300 participants in 4 patient groups

Olfactory Stimulation Group
Experimental group
Treatment:
Behavioral: Olfactory stimulation
TI Stimulation Group
Experimental group
Treatment:
Biological: Temporal Interference,TI
Olfactory-TI Stimulation Group
Experimental group
Treatment:
Combination Product: Olfactory-TI Stimulation
Sham Control Group
Sham Comparator group
Treatment:
Combination Product: Sham Control

Trial contacts and locations

0

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Data sourced from clinicaltrials.gov

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