Effects of 40-Hz transcranial alternating current stimulation on cognition and neural markers in Alzheimer's disease: a randomized, sham-controlled trial
Summary
In this randomized, double-blind, sham-controlled trial, 39 participants with Alzheimer's disease received either 40-Hz tACS (n=20) or sham stimulation (n=19) targeting the left dorsolateral prefrontal cortex. Compared with sham, 40-Hz tACS was associated with improved global cognition, reduced depressive symptoms, increased frontal-central theta power, enhanced theta band hippocampal-prefrontal connectivity, and exploratory reductions in plasma p-tau217 and p-tau181.
Why it matters
Gamma-frequency (40-Hz) brain stimulation has emerged as a promising therapeutic approach for Alzheimer's disease. This trial demonstrates target engagement and a trajectory-level cognitive signal, supporting the continued investigation of gamma entrainment as a potential disease-modifying intervention for AD. The neural mechanism and biomarker changes provide a foundation for optimizing stimulation protocols.
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