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A new study published in the Journal of Neurosurgery highlights the potential of focused ultrasound technology in treating Alzheimer’s disease. The clinical trial demonstrated that repetitive opening of the blood-brain barrier using focused ultrasound reduced amyloid plaques—protein buildups linked to Alzheimer’s—without using Alzheimer’s medications. In addition to clearing plaques, the treatment led to improvements in neuropsychiatric symptoms, such as anxiety and irritability, for the majority of participants, showing promise as a new approach to managing this debilitating condition.
Jin Woo Chang, a neurosurgeon at Korea University Anam Hospital, led the study alongside neurologists from Yonsei University. The researchers aimed to explore the potential of focused ultrasound to tackle Alzheimer’s more effectively.
Alzheimer’s disease, a progressive neurodegenerative disorder, is marked by cognitive decline and the accumulation of harmful amyloid-beta plaques in the brain. These plaques have been a primary target for therapies, but existing treatments often struggle to effectively deliver drugs to the brain due to the protective blood-brain barrier. Focused ultrasound offers a way to temporarily open this barrier, enabling access to deeper brain regions.
The study enrolled six women aged 50 to 85 diagnosed with Alzheimer’s. Participants underwent three sessions of blood-brain barrier opening at two-month intervals using the ExAblate Neuro 220 kHz low-intensity focused ultrasound system. A microbubble agent, DEFINITY®, was injected intravenously during the procedure to enhance the ultrasound’s effect. This treatment targeted both frontal lobes, focusing on areas of the brain commonly affected by Alzheimer’s. Before and after the sessions, researchers used advanced imaging techniques and neuropsychiatric assessments to evaluate changes in amyloid levels and mental health symptoms.
The study achieved a significant milestone by safely opening a blood-brain barrier volume of 43.1 cubic centimeters—double the volume of previous trials. Importantly, this approach reduced amyloid plaques in four of the six participants. Neuropsychiatric symptoms, measured through the Caregiver-Administered Neuropsychiatric Inventory, improved in five participants, with reductions in issues like agitation, delusions, and anxiety. No serious side effects were reported, and participants tolerated the procedure well, despite its duration and the requirement to remain still.
Chang and his colleagues emphasized that the study’s design isolated the effects of the blood-brain barrier opening alone, without combining it with medications. This allowed them to assess whether focused ultrasound could independently reduce amyloid plaques and improve symptoms. The findings suggest that even without drugs, clearing plaques may positively impact Alzheimer’s symptoms, particularly those related to behavior and mood.
“We developed this protocol to provide optimal benefit and to test the technology in larger regions of the brain that are affected by Alzheimer’s disease,” said Chang. “This study begins to provide a more complete understanding of the effects of blood-brain barrier opening alone. It will serve as the basis for future trials comparing any potential benefit of adding drug delivery the affected areas of the brain.”
The research was funded by the Focused Ultrasound Foundation.
“This study is critical to the field as a whole,” said Foundation Chairman Neal F. Kassell, MD. “Knowing what happens with blood-brain barrier opening in the absence of drugs in patients with Alzheimer’s disease adds a tremendous amount of knowledge to the field and lays the groundwork for further exploration with multiple focused ultrasound mechanisms of action. Focused ultrasound is a new technology that is now being explored in patients with Alzheimer’s disease, a field that has remained stagnant in terms of therapeutic options over the past several decades.”
However, the study’s small sample size limits the generalizability of its results. With only six participants, further research with larger groups is needed to confirm these findings. Additionally, while neuropsychiatric symptoms improved, the study did not observe significant cognitive improvements, such as better memory or problem-solving abilities. This may be because the treatment focused solely on the frontal lobes, while regions like the hippocampus—critical for memory—were not targeted.
Looking ahead, researchers plan to build on these results by conducting larger trials. Future studies will explore the effects of opening even larger brain regions and combining focused ultrasound with Alzheimer’s medications to enhance treatment outcomes. These efforts aim to refine the technique and maximize its potential benefits for patients at various stages of the disease.
The study, “Repetitive and extensive focused ultrasound–mediated bilateral frontal blood-brain barrier opening for Alzheimer’s disease,” was authored by Byoung Seok Ye, Kyung Won Chang, Sungwoo Kang, Seun Jeon, and Jin Woo Chang.
