Efficacy and safety of focused ultrasound-mediated blood-brain barrier opening in Alzheimer's disease: A systematic review and meta-analysis

Abstract

Background: Alzheimer's disease (AD) manifests as an insidiously progressive neurodegenerative pathology, wherein the current therapeutic armamentarium remains constrained to symptomatic management, highlighting an urgent need for innovative therapies. Objective: This meta-analysis systematically conducts an assessment of the safety and efficacy of focused ultrasound (FUS)-mediated reversible blood-brain barrier opening (BBBO) in AD, while further exploring its potential associations with cognitive function and amyloid-β (Aβ) deposition in patients. Methods: PubMed, Embase, CNKI, Cochrane Library, and Web of Science were searched in this study. The study protocol has been registered with PROSPERO (registration number, CRD42024585286). ROBINS-I tool was used to assess the risk of bias, followed by further data analysis. Results: Fifty-seven AD patients from eight distinct clinical studies were systematically incorporated into the meta-analytical framework. The time span was from 2018 to 2023. After FUS-mediated BBBO, the analysis demonstrated significant outcomes of FUS for both safety (OR: 0.88; 95% CI: 0.75–0.98, p < 0.01) and efficacy (OR: 0.91; 95% CI: 0.61–1.00, p < 0.01). There was no deterioration of cognitive function after surgery, and the observed adverse events were minor and temporary in nature. Conclusions: This meta-analysis underscores the potential of FUS as a non-invasive, safe, and effective method for enhancing BBB permeability in AD patients, offering a promising avenue for targeted drug delivery and disease modification. Future multicenter studies with larger sample sizes and standardized methodologies are warranted to confirm these results and explore the integration of FUS with existing and emerging AD therapies.