Potential Mechanism and Efficacy Evaluation of Transcranial Focused Ultrasound Therapy for Alzheimer's Disease.

Abstract

Background: Transcranial focused ultrasound (TFU) is emerging as a promising non-invasive therapy capable of blood-brain barrier (BBB) opening. TFU potentially allows the transfer of therapeutic agents to targeted brain areas for patients affected with Alzheimer's disease (AD).

New method: The efficacy and mechanism of TFU in modulating BBB permeability in key brain regions, including the hippocampus and frontal lobe, are investigated in this research. A total of 20 participants aged 60-85 years were involved with AD. The treatment protocol involved three TFU sessions, spaced three weeks apart. The research encompasses pre-assessment and post-assessment of treatment with follow-up ranging from 5 to 12 months.

Results: Statistical analysis involved paired t-tests to compare pre- and post-treatment cognitive scores, and ANOVA to predict significant differences in amyloid reduction across different brain regions, with the high decrease observed in the hippocampus. Multivariate Analysis (MANOVA) to explore the combined effect of cognitive and amyloid data. Linear Regression Analysis to predict cognitive improvement from amyloid plaque reduction. Longitudinal analysis for time-to-event analysis assessing the durability of effects over time.

Comparison with existing methods: Florbetaben Positron Emission Tomography (PET) scans demonstrated a reduction in β-amyloid plaque burden, with a 15% average decrease in the treated brain regions. No adverse effects on disease progression were observed up to 1 year after treatment.

Conclusion: This analysis presents the largest cohort of AD patients treated with TFU, with the longest follow-up to date. The treatment demonstrated safety and feasibility, with reversible BBB opening in multiple brain regions.