A phase II clinical trial has revealed that personalized transcranial magnetic stimulation (TMS) can significantly slow the progression of Alzheimer's disease. The study, presented at the Clinical Trials on Alzheimer's Disease (CTAD) annual meeting, focused on stimulating the precuneus within the default mode network using a tailored TMS protocol.
Giacomo Koch, MD, PhD, from the University of Ferrara in Italy, highlighted the rationale behind targeting the default mode network, noting it's one of the earliest brain networks affected by Alzheimer's, with beta-amyloid and tau accumulation initiating in these areas. The personalized approach combines neuro-navigation for precise targeting and TMS with electroencephalography (EEG) to optimize stimulation parameters for each patient.
Personalized TMS Protocol
The TMS protocol involves an initial 2-week "boosting phase" with daily sessions from Monday to Friday, followed by an intensive phase and a maintenance phase with weekly treatments for the subsequent 50 weeks. This regimen aims to enhance connectivity within the targeted brain network.
Promising Clinical Results
Despite the relatively small sample size—32 patients were analyzed out of an initial enrollment of 48 due to COVID-related attrition—the study demonstrated statistically significant results. The primary endpoint, CDR (Clinical Dementia Rating Scale)-Sum of Boxes, showed a slowing in the progression of clinical scores. Secondary outcomes further supported these findings.
"The autonomy of daily living was nearly unchanged after 1 year of therapy. And this is very important for quality of life, patients' autonomy, and caregivers' burden," Koch explained. Significant effects were also observed in the ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale), which assesses memory and cognitive function, as well as improvements in behavioral disturbances measured by the Neuropsychiatric Inventory (NPI).
Neurophysiological Support
Neurophysiological data indicated that patients treated with repetitive TMS, compared to placebo, exhibited increased connectivity within the default mode network. Furthermore, a correlation was found between this increased connectivity and clinical gains as measured by the CDR-Sum of Boxes, reinforcing the potential of this therapeutic approach.
