Home-based transcranial alternating current stimulation (tACS) in Alzheimer’s disease: rationale and study design

Background: Gamma (γ) brain oscillations are dysregulated in Alzheimer's disease (AD) and can be modulated using transcranial alternating stimulation (tACS). In the present paper, we describe the rationale and design of a study assessing safety, feasibility, clinical and biological efficacy, and predictors of outcome of a home-based intervention consisting of γ-tACS over the precuneus. Methods: In a first phase, 60 AD patients will be randomized into two arms: ARM1, 8-week precuneus γ-tACS (frequency: 40 Hz, intensity: 2 mA, duration: 5 60-min sessions/week); and ARM2, 8-week sham tACS (same parameters as the real γ-tACS, with the current being discontinued 5 s after the beginning of the stimulation). In a second phase, all participants will receive 8-week γ-tACS (same parameters as the real γ-tACS in the first phase). The study outcomes will be collected at several timepoints throughout the study duration and include information on safety and feasibility, neuropsychological assessment, blood sampling, electroencephalography, transcranial magnetic stimulation neurotransmitter measures, and magnetic resonance imaging or amyloid positron emission tomography. Results: We expect that this intervention is safe and feasible and results in the improvement of cognition, entrainment of gamma oscillations, increased functional connectivity, reduction of pathological burden, and increased cholinergic transmission. Conclusions: If our expected results are achieved, home-based interventions using γ-tACS, either alone or in combination with other therapies, may become a reality for treating AD. Trial registration: PNRR-POC-2022-12376021.