TRanscranial AlterNating current Stimulation FOR patients with Mild Alzheimer's Disease (TRANSFORM-AD study): Protocol for a randomized controlled clinical trial.

Introduction: Recently, transcranial alternating current stimulation (tACS), which can interact with ongoing neuronal activity, has emerged as a potentially effective and promising treatment for Alzheimer's disease (AD), and the 40 Hz gamma frequency was suggested as a suitable stimulation frequency for AD. Methods: The TRANSFORM-AD study is a double-blind, randomized-controlled trial that will include 40 individuals with mild AD. Eligible patients need to have amyloid beta (Abeta) loads examined by Pittsburgh compound B (PiB) positron emission tomography (PET) or decreased Abeta level in cerebrospinal fluid. Participants will be randomized into either a 40 Hz tACS group or a sham stimulation group. Both groups will undergo 30 one-hour sessions across 3 weeks (21 days). The outcome measures will be assessed at baseline, at the end of the intervention, and 3 months after the first session. The primary outcome is global cognitive function, assessed by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), and the secondary outcomes include changes in other neuropsychological assessments and in PiB-PET, structural magnetic resonance imaging (MRI), resting electroencephalography (EEG), and simultaneous EEG-functional MRI (EEG-fMRI) results. Results: The trial is currently ongoing, and it is anticipated that recruitment will be completed in June 2021. Discussion: This trial will evaluate the efficacy and safety of 40 Hz tACS in patients with AD, and further explore the potential mechanisms by analyzing amyloid deposits using PiB-PET, brain volume and white matter integrity by structural MRI, and neural activity by EEG and EEG-fMRI.