A RANDOMISED clinical trial has demonstrated that transcranial pulse stimulation (TPS), a form of ultrasound neuromodulation , improves cognitive function and brain network activity in younger patients with Alzheimer’s disease (AD), offering promise as a novel add-on therapy.
Alzheimer’s disease remains a leading cause of dementia worldwide, with limited treatment options available to slow cognitive decline. Ultrasound neuromodulation has emerged as a potential therapeutic approach, though its efficacy and safety in AD are not yet fully established. This study evaluated whether TPS, a non-invasive technique delivering ultrasonic pulses to brain regions associated with memory and attention, could enhance cognitive performance and neural connectivity in patients already receiving standard AD treatments.
The double-blind, sham-controlled trial involved 60 patients aged 51–82 (mean 70.7 years, 50% female) diagnosed with AD. Participants were randomised to receive either verum TPS followed by sham treatment or vice versa, with each cycle comprising six sessions over two weeks. Cognitive function was assessed using the CERAD corrected total score (CTS), alongside functional MRI to measure brain activation and connectivity. In the intention-to-treat analysis, younger patients (≤70 years) showed significant cognitive improvement with verum TPS, with CTS increasing by a mean of 3.91 points three months post-treatment, compared to a 1.83-point decrease under sham conditions (p=0.005; ηp²=0.16). Older patients (>70 years) saw less pronounced benefits. Functional MRI revealed enhanced memory-associated activation in the precuneus, visual, and frontal areas, alongside increased connectivity in the dorsal attention network. Verum TPS also reduced depressive symptoms in the per-protocol analysis (Beck Depression Inventory-II scores decreased from 7.27 to 5.27, p=0.008; ηp²=0.23). Adverse effects were mild, primarily transient depression, with no major neuropathological changes detected.
These findings suggest TPS could serve as a safe adjunct therapy for AD, particularly in younger patients. For clinical practice, TPS may offer a non-pharmacological option to complement existing treatments, though further research is needed to optimise protocols and validate age-specific responses. Future studies should explore long-term effects, ideal dosing, and mechanisms underlying TPS’s neurobiological effects. Larger trials across diverse populations are essential to confirm these results and establish guidelines for integrating TPS into routine care.
Katrina Thornber, EMJ
Reference
Matt E et al. Ultrasound neuromodulation with transcranial pulse stimulation in alzheimer disease: a randomized clinical trial. JAMA Netw Open. 2025;8(2):e2459170.
