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

Abstract 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 β (Aβ) loads examined by Pittsburgh compound B (PiB) positron emission tomography (PET) or decreased Aβ 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.