Novel Personalized Non Invasive Combined Magnetic and Electrical Stimulation of the DMN in Mild AD Patients

Alzheimer's disease (AD) is increasingly recognized as a disorder marked by early synaptic dysfunction and disrupted brain network connectivity, beyond the traditional focus on amyloid pathology. Synaptic plasticity (crucial for learning and memory) is compromised in AD and represents a promising therapeutic target. In particular, alterations in the Default Mode Network (DMN), especially in regions like the precuneus, suggest that restoring connectivity and enhancing plasticity may improve cognitive outcomes. This project proposes a novel, precision-delivered non-invasive brain stimulation protocol that combines repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) over the DMN. The intervention will be evaluated through cognitive testing, blood-based biomarkers, MRI and TMS-EEG, alongside immersive virtual environments to assess sensorimotor and cognitive function. This approach aims to test neuromodulation strategies capable of slowing neurodegeneration and supporting early detection and rehabilitation in AD.

NCT Number	NCT07075770
Lead Sponsor	I.R.C.C.S. Fondazione Santa Lucia Collaborators: IRCCS Centro Neurolesi Bonino Pulejo
Conditions	Alzheimer Disease
Enrollment	60 participants
Start Date	2025-01-01
Primary Completion	2027-06-30 (estimated)
Study Completion	2027-08-31 (estimated)
Updated on ClinicalTrials.gov	2026-01-13