Abstract
Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer’s disease (AD) by opening the blood–brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), 18F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall (p = 0.03) and recognition memory (p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus (p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman’s ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.
Highlights
Alzheimer’s disease (AD) is characterized by progressive neurodegeneration with cognitive and functional declines [1]
Increases in regional cerebral metabolic rate of glucose (rCMRglu) in the hippocampus campus were correlated with improvement of recognition memory
Results were correlated with improvement of recognition memory
Summary
Alzheimer’s disease (AD) is characterized by progressive neurodegeneration with cognitive and functional declines [1]. Low-intensity transcranial focused ultrasound (tFUS) applies acoustic energy to specific brain regions, with high spatial resolution and penetration depth [6]. Low-intensity transcranial focused ultrasound (tFUS) applies acoustic energy to2specific brain regions, with high spatial resolution and penetration depth [6]. It can excite or suppress neuronal activity without thermal damage, in addition to transiently opening the blood–brain barrier (BBB). BBB disruption, regional gional metabolic rate of glucose (rCMRglu), and on cognitive function the in patients cerebral metabolic rate of glucose (rCMRglu), and cognitive function in patients with with AD For this ongoing research effort, our previous case report first described theAD. We added six additional test subjects to the cohort, such that the present the present analysis makes use of data from all ten test subjects—six new ones described analysis use offour datafrom fromour all ten test subjects—six here andmakes the original published report [16].new ones described here and the original four from our published report [16]
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