Personalized, home-based transcranial alternating current stimulation for memory improvement in mild cognitive impairment: randomized, sham-controlled clinical trial protocol.

BACKGROUND: Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD) and represents a critical window for interventions aimed at slowing neurodegenerative progression. Disruptions in neural oscillatory activity are key contributors to memory dysfunction in MCI and AD. Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique that entrains neural oscillations at specific frequencies, potentially restoring network dynamics underlying memory. METHODS: The MemStim study is a randomized, sham-controlled, parallel-arm, double-blind clinical trial evaluating the efficacy of personalized, home-based gamma-frequency tACS over the left angular gyrus, delivered 5 days a week for 4 weeks, in individuals with MCI. Safety and tolerability are monitored throughout the intervention. Forty participants aged ≥55 years with clinically diagnosed MCI will be recruited at the Geneva University Hospitals and randomized to active or sham stimulation. All participants undergo baseline and post-stimulation assessments, including cognitive testing, structural MRI, and high-density EEG (hdEEG). Individual MRI-based electric-field modeling personalizes stimulation montages targeting the left angular gyrus, a key node of the memory network. OUTCOMES: The primary outcome is the change in global cognitive function measured by the Montreal Cognitive Assessment (MoCA) from baseline to post-intervention. Secondary outcomes include changes in gamma-band oscillatory power measured with hdEEG. Exploratory EEG analyses will examine spectral, temporal, and spatial brain dynamics. Cognitive assessments are repeated 3 months post-intervention to evaluate persistence of effects. DISCUSSION: This trial investigates whether personalized gamma-frequency tACS can modulate hdEEG measures of resting-state brain activity and improve memory function in MCI. By integrating individualized stimulation targeting, electrophysiological biomarkers, and remotely supervised home-based delivery, the MemStim study aims to advance personalized neuromodulation as a scalable therapeutic strategy for early intervention in cognitive decline. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05708001.