A-03: Transcranial Pulse Stimulation as an Emerging Intervention for Alzheimer’s Disease: A Sham-Controlled Pilot Study

Abstract

Objective: Effective treatment options for Alzheimer’s disease (AD) remain limited. Transcranial Pulse Stimulation (TPS) is a novel, noninvasive neuromodulation technique that uses ultrashort, low-intensity ultrasound pulses with high spatial precision and focality, including in deeper tissue layers. Previous research indicates neuropsychological improvement and structural brain changes following TPS in AD patients. Method/Data Selection: To confirm these findings, we are conducting a randomized, sham-controlled study recruiting 20 participants aged 65–100: 10 with mild AD and 10 normal-aging adults. Participants are randomly assigned to active or sham stimulation and receive six sessions over two weeks targeting the precuneus, the dorsolateral prefrontal cortex, and the lateral parietal nodes of the default mode network. Multi-modal MRI, blood-derived AD biomarkers, and comprehensive neurocognitive assessment are collected at baseline and at post-stimulation follow-ups. Results/Data Synthesis: To date, six mild AD participants (three active, three sham) have completed the protocol. Although the study remains blinded, exploratory analyses of the ADAS-Cog-plus battery revealed interindividual variability (-3.34 to +3.33 points). Three participants showed cognitive improvement, one remained stable, and two showed either cognitive decline or minimal worsening. Preliminary structural neuroimaging alterations are currently available for five participants and align with these behavioral findings in 60% of cases. Conclusions: The preliminary pattern of cognitive change suggests possible intervention-related effects. Continued data collection will determine whether these patterns persist and whether the cognitive improvements are indeed associated with the active stimulation condition.