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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.