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.
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Change in Olfactory Sensitivity (TDI score)
Timeframe: Baseline; 30 minutes after Session 1; 30 minutes after Session 5; 30 minutes after Session 10; 1 week after Session 10.
Path Integration - Angle Deviation
Timeframe: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Path Integration - Distance Deviation
Timeframe: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Path Integration - Composite Accuracy (M_ROC_AUC)
Timeframe: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Change in Cognitive Performance (MoCA-B)
Timeframe: Baseline; 5 minutes after Session 10.