Ultrasound-Induced Blood–Brain Barrier Opening in Alzheimer’S Disease: A Systematic Review of Clinical Studies Publisher Pubmed



Niknam N ; Songhori N ; Nekahi N ; Kavian M ; Khosravi F ; Fard A M ; Moshiri Y ; Haghshenas N ; Sadegh M H ; Torabi P
Source: Aging Clinical and Experimental Research Published:2026

Abstract

Background: Focused ultrasound (FUS) has emerged as a non-invasive approach to transiently open the blood–brain barrier (BBB) and facilitate therapeutic delivery in Alzheimer’s disease (AD). This systematic review evaluates current clinical evidence regarding the feasibility, safety, and reported biological and clinical outcomes of FUS-mediated BBB opening. Method: A systematic search of PubMed, Scopus, and Web of Science was conducted in accordance with PRISMA 2020 guidelines and supplemented by Google Scholar. Human clinical studies employing FUS-induced BBB opening in AD were included. Risk of bias was assessed using the ROBINS-I tool for non-randomized studies. Results: From an initial screening of 587 records, 27 studies met the inclusion criteria. Across these studies, FUS-mediated BBB opening was generally feasible and well tolerated, with no reports of irreversible procedure-related adverse events. Reported adverse effects were typically mild and transient, including localized headache, fatigue, or imaging-detected edema. Exploratory findings included heterogeneous changes in cognitive measures and regional amyloid-β biomarkers assessed by neuroimaging or cerebrospinal fluid analysis. Substantial variability in study design, target regions, sonication parameters, and outcome measures limited quantitative synthesis and definitive interpretation. Conclusion: Current clinical evidence supports the short-term feasibility and safety of FUS-mediated BBB opening in AD. However, the available data remain preliminary, and well-designed randomized controlled trials with larger cohorts, standardized imaging and cognitive endpoints, and longer follow-up are required to determine therapeutic efficacy and sustained clinical benefit. © The Author(s) 2026.