Background: The purpose of this study was to evaluate the safety and efficacy of low-intensity tFUS under the threshold for BBB disruption in patients with AD. In addition, we assessed changes in the regional cerebral metabolic rate of glucose (rCMRglu) using F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET) and cognitive function after tFUS. Methods: Eight AD patients were recruited. We applied low-intensity tFUS to the right hippocampus for 3 minutes using an image-guided tFUS system. For multi-modal neuroimaging guidance, MRI and CT data were spatially co-registered using the maximization of normalized mutual information. The subjectspecific coordinates of the hippocampus in the right hemisphere were identified as the tFUS target location. Results: Radiological evidence of contrast enhancement associated with BBB opening was not found in neither the visual inspection nor the ICA of the DCE-MRI data. No adverse events were observed during the hospitalization and follow-up outpatient visits for 5 to 24 months. The immediate recall and recognition memory on the SVLT were significantly improved after the sonication. The PET analysis showed the increased level of rCMRglu in the right hippocampus. Conclusions: Application of low-intensity tFUS to the hippocampus with MB did not open blood brain barrier but increased hippocampal glucose metabolism and memory function.