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.
Patients with a diagnosis of AD according to IWG criteria
20 > MMSE < 28
Patients with CSF specific biomarker profile or with a positive Amyloid Pet Scan consistent with the presence of amyloid pathology
Global Clinical Dementia Rating (CDR) ≤1
Failure to undergo screening or baseline exams
Hospitalization or change in chronic concomitant medications one month before the screening or during the screening period
other primary degenerative dementia (Lewy body dementia, frontotemporal dementia, Huntington's disease, Creutzfeldt-Jakob disease, Down syndrome, etc.);
other neurodegenerative conditions (Parkinson's disease, amyotrophic lateral sclerosis, etc.);
I.R.C.C.S. Fondazione Santa Lucia
Lead sponsor
IRCCS Centro Neurolesi Bonino Pulejo
Collaborator