Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment

Abstract

Introduction: Ultrasound-based brain stimulation is a novel, non-invasive therapeutic approach to precisely target regions of interest. Data from a first clinical trial of patients with Alzheimer's disease (AD) receiving 2-4 weeks transcranial pulse stimulation (TPS) have shown memory and cognitive improvements for up to 3 months, despite ongoing state-of-the-art treatment. Importantly, depressive symptoms also improved. Methods: We analyzed changes in Beck Depression Inventory (BDI-II) and functional connectivity (FC) changes with functional magnetic resonance imaging in 18 AD patients. Results: We found significant improvement in BDI-II after TPS therapy. FC analysis showed a normalization of the FC between the salience network (right anterior insula) and the ventromedial network (left frontal orbital cortex). Discussion: Stimulation of areas related to depression (including extended dorsolateral prefrontal cortex) appears to alleviate depressive symptoms and induces FC changes in AD patients. TPS may be a novel add-on therapy for depression in AD and as a neuropsychiatric diagnosis.