Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer's disease
Related Experiment Video
Updated: Oct 9, 2025
Transcranial Pulse Stimulation for Alzheimer's Patients
Published on: April 4, 2025
Giulia Sprugnoli1,2, Fanny Munsch3, Davide Cappon1
1Berenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Background:
Alzheimer's disease (AD) is associated with alterations in cortical perfusion that correlate with cognitive impairment. Recently, neural activity in the gamma band has been identified as a driver of arteriolar vasomotion while, on the other hand, gamma activity induction on preclinical models of AD has been shown to promote protein clearance and cognitive protection.
Methods:
In two open-label studies, we assessed the possibility to modulate cerebral perfusion in 15 mild to moderate AD participants via 40Hz (gamma) transcranial alternating current stimulation (tACS) administered 1 h daily for 2 or 4 weeks, primarily targeting the temporal lobe. Perfusion-sensitive MRI scans were acquired at baseline and right after the intervention, along with electrophysiological recording and cognitive assessments.
Results:
No serious adverse effects were reported by any of the participants. Arterial spin labeling MRI revealed a significant increase in blood perfusion in the bilateral temporal lobes after the tACS treatment. Moreover, perfusion changes displayed a positive correlation with changes in episodic memory and spectral power changes in the gamma band.
Conclusions:
Results suggest 40Hz tACS should be further investigated in larger placebo-controlled trials as a safe, non-invasive countermeasure to increase fast brain oscillatory activity and increase perfusion in critical brain areas in AD patients.
Trial Registration:
Studies were registered separately on ClinicalTrials.gov ( NCT03290326 , registered on September 21, 2017; NCT03412604 , registered on January 26, 2018).
