tACS Connectivity Trial in Early Alzheimer's

SUMMARY

# tACS Connectivity Trial in Early Alzheimer's ## Background and Rationale Alzheimer's disease progression follows a network-based model where pathological tau propagates along functional connectivity pathways. Recent evidence demonstrates that hyperconnected brain regions serve as hubs for early tau accumulation, creating a self-reinforcing cycle where elevated connectivity accelerates pathological spread, which in turn drives further hyperconnectivity. This pathophysiological mechanism suggest

METHODOLOGY NOTES

Phase 1 (Weeks -4 to 0): Comprehensive screening including neuropsychological assessment (ADAS-Cog, MoCA), structural/functional MRI acquisition, tau PET imaging, and CSF biomarker collection (n=120 early AD patients, n=40 healthy controls). Individual connectivity matrices generated using seed-based analysis targeting default mode and salience networks. Phase 2 (Week 0): Randomization to active tACS (n=60) or sham stimulation (n=60) groups using computer-generated sequences. Baseline EEG recording during resting state and cognitive tasks. Phase 3 (Weeks 1-12): Intervention delivery using personalized montages targeting hyperconnected regions identified in Phase 1. Active group receives 40 Hz sinusoidal stimulation at 2 mA peak-to-peak intensity, 20-minute sessions, 5 days/week. Sham group receives identical setup with 30-second ramp-up/down only. Weekly safety assessments and adherence monitoring. Phase 4 (Weeks 4, 8, 12): Interim assessments including cognitive testing, EEG connectiv