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  • [J Pers Med.] Short-Term Efficacy of Transcranial Focused Ultrasound to the Hippocampus in Alzheimer's Disease: A Preliminary Study

    가톨릭대 / 정현석, 송인욱*, 정용안*

  • 출처
    J Pers Med.
  • 등재일
    2022 Feb 9
  • 저널이슈번호
    12(2):250. doi: 10.3390/jpm12020250.
  • 내용

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    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.

     

     

    Affiliations

    Hyeonseok Jeong  1   2 , In-Uk Song  3 , Yong-An Chung  1   2 , Jong-Sik Park  3 , Seung-Hee Na  3 , Jooyeon Jamie Im  1 , Marom Bikson  4 , Wonhye Lee  5 , Seung-Schik Yoo  5
    1 Department of Nuclear Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea.
    2 Department of Radiology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea.
    3 Department of Neurology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea.
    4 Department of Biomedical Engineering, The City College of New York, New York, NY 10031, USA.
    5 Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

  • 키워드
    Alzheimer’s disease; blood–brain barrier; cognition; regional cerebral metabolic rate of glucose; transcranial focused ultrasound.
  • 연구소개
    전임상 연구에 따르면, 저강도집중초음파 자극은 혈액뇌장벽을 열고 아밀로이드반을 감소시키고 인지기능을 개선시키는 가능성이 있었다. 본 연구는 총 10명 알츠하이머병 환자를 대상으로 뇌 해마에 직접 저강도집중초음파자극을 공여한 최초의 탐색 임상 연구로, 치료의 안정성 및 임상적 유용성을 신경심리검사, 뇌자기공명영상, 뇌포도당양전자단층촬영술 등을 통해 평가하였다. 평가 결과 언어학습테스트에서 즉각적인 회상과 인지기억이 향상되었고, 직접 자극한 뇌 해마의 포도당대사가 증가되었다. 더불어 해마의 포도당대사 증가는 인지기억의 개선과 유의한 상관관계가 있었다. 결론적으로 알츠하이머병 환자에서 저강도집중초음파 자극을 통해 안전하게 포도당대사를 증가시키고 기억도 향상 시킬 수 있는 가능성을 확인할 수 있었다.
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