Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study

Objective: To assess whether exposure to non-invasive brain stimulation with transcranial alternating current stimulation at y frequency (y-tACS) applied over Pz (an area overlying the medial parietal cortex and the precuneus) can improve memory and modulate cholinergic transmission in mild cognitive impairment due to Alzheimer's disease (MCI-AD). Methods: In this randomized, double-blind, sham controlled, crossover pilot study, participants were assigned to a single 60 min treatment with exposure to y-tACS over Pz or sham tACS. Each subject underwent a clinical evaluation including assessment of episodic memory pre- and post-y-tACS or sham stimulation. Indirect measures of cholinergic transmission evaluated using transcranial magnetic stimulation (TMS) pre- and post-y-tACS or sham tACS were evaluated. Results: Twenty MCI-AD participants completed the study. No tACS-related side effects were observed, and the intervention was well tolerated in all participants. We observed a significant improvement at the Rey auditory verbal learning (RAVL) test total recall (5.7 [95% CI, 4.0 to 7.4], p < 0.001) and long delayed recall scores (1.3 [95% CI, 0.4 to 2.1], p 1/4 0.007) after y-tACS but not after sham tACS. Face-name associations scores improved during y-tACS (4.3 [95% CI, 2.8 to 5.8], p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission evaluated with TMS, increased only after y-tACS (0.31 [95% CI, 0.24 to 0.38], p < 0.001) but not after sham tACS. Conclusions: exposure to y-tACS over Pz showed a significant improvement of memory performances, along with restoration of intracortical connectivity measures of cholinergic neurotransmission, compared to sham tACS. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license