Feasibility and safety of repeated low-intensity ultrasound in amyloid PET-positive early Alzheimer's disease: A prospective pilot study

BackgroundLow-intensity ultrasound (LIUS) is a potential noninvasive neuromodulatory approach for Alzheimer's disease (AD), but clinical evidence on repeated stimulation in biomarker-confirmed early AD remains limited.ObjectiveTo evaluate the feasibility, safety, and exploratory clinical effects of a 4-week repeated LIUS protocol in amyloid positron emission tomography (PET)-positive early AD.MethodsTwenty patients with amyloid PET-positive prodromal AD or mild AD dementia underwent LIUS targeting bilateral frontal and temporal regions three times weekly for 4 weeks. Safety was assessed by neurological examinations and brain magnetic resonance imaging (MRI). Exploratory outcomes included the Trail Making Test-Black & White (TMT-B&W) parts A and B, Attention Questionnaire Scale (AQS), Korean version of Quality of Life (KQoL), Mini-Mental State Examination (MMSE), and Neuropsychiatric Inventory (NPI). Resting-state functional MRI was analyzed in an exploratory subset.ResultsNo severe adverse events occurred, and post-treatment MRI showed no intracerebral hemorrhage, microbleeding, or brain edema. Completion times decreased on TMT-B&W part A (105.3 ± 63.3 versus 84.2 ± 46.6 s, p = 0.012) and part B (280.1 ± 139.9 versus 212.8 ± 59.7 s, p = 0.038). NPI scores also decreased (9.8 ± 14.7 versus 4.5 ± 8.8, p = 0.006). KQoL, AQS, and MMSE did not change significantly.ConclusionsRepeated LIUS over 4 weeks was feasible and well tolerated in amyloid PET-positive early AD. Exploratory changes in executive function and neuropsychiatric symptoms were observed; however, the single-arm design precludes causal inference. Randomized, sham-controlled studies are warranted to determine the therapeutic potential of LIUS.