To determine whether high-frequency transcranial magnetic stimulation improves memory retention in early-stage Alzheimer’s Disease (ES-AD)

AD is a neurodegenerative condition associated with disruption of large-scale brain networks (LSBNs). Repeated theta burst stimulation (rTBS) induces plasticity in LSBNs and slows cognitive decline in AD. Non-invasive neurostimulation to the default mode network (DMN) is associated with neuropsychiatric benefits. Area 8AV, identified via the Human Connectome Project, is a DMN node accessible to rTBS. The Seattle-Groningen Memory Assessment (SGMA) is a model-based evaluation designed to avoid practice effects.  We evaluated the impact on memory of rTBS to area 8AV in patients with early-stage AD.

A single-arm, single-blind, sham-controlled crossover study was conducted in 8 biomarker-confirmed, ES-AD  patients (mean age 76.3; 50% female; mean MoCA 21.2). Structural/functional MRI, MoCA, GAD-7, and GDS were collected at baseline and at 4 weeks post-treatment. Participants received six 10-min sessions of rTBS or sham for 5 days, which was then switched after a 4-week washout.  SGMA was scored at baseline and weekly during washout. The cognitive endpoint was change in SGMA score from baseline. A linear mixed-effect model with anxiety and depression scores as covariates was used.

rTBS to area 8AV resulted in a mean 10.62% improvement in memory retention in the four weeks following treatment (p= .02). Improvements were largest (13.50%) in the week following rTBS, but returned to baseline by week 4. Sham had no effects on cognition.  Anxiety and depression scores didn’t modulate the effect, nor were they affected by treatment type (p > .27). 

rTBS to the DMN via region 8AV is a safe and potentially promising treatment for memory loss in early-stage AD. Our preliminary findings suggest transient benefits of this intervention. Further studies are necessary to determine long-term efficacy.