The goal of this study is to investigate whether Low Intensity Focused Ultrasound Pulsation (LIFUP) targeting a part of the brain involved in memory will have an affect on brain activity and whether it may improve memory in people with Mild Cognitive Impairment and Mild Alzheimer's Disease.
The main questions the study seeks to answer are:
1. Can LIFUP increase brain activity in the targeted area? 2. Can LIFUP improve memory in people with MCI and mild AD? 3. Can LIFUP improve connectivity of memory networks in the brain?
Participants in this study will complete MRIs and memory testing, and receive Low Intensity Focused Ultrasound to a part of their brain involved in memory (the entorhinal cortex).
Amnestic MCI or Mild Alzheimer's diagnosis
Age 50-90
English-speaking
Ability to provide informed consent
Participation in another clinical trial
Active use of immunotherapeutic medications for cognition (Aduhelm, Leqembi, Kisunla)
Moderate to Severe Alzheimer's
Inability to provide informed consent
Parallel
Low-Intensity Focused Ultrasound Pulsation (LIFUP)
DeviceLow intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)
Change in Perfusion Arterial Spin Labeling (ASL) fMRI Signal throughout Brain
Perfusion ASL fMRI data will be collected before and after sonication. Analyses will assess the statistical relationship between ASL signal throughout the brain pre and post sonication.
Changes in BOLD-related functional connectivity from baseline in fMRI brain scan to 40 minutes.
Primary outcomes for proof of mechanism that may be depicted in the fMRI scans may include changes in BOLD-related functional connectivity increases within the DMN including regions functionally connected to the target. BOLD data will be collected before, during, and following LIFUP sonication. Analyses will assess any changes in BOLD signal in the brain following sonication.
Change in Brief Visual Memory Test Scores
Potential LIFUP-related changes in memory will be assessed via neuropsychological assessments including the Brief Visual Memory Tests (BVMT). Scores range from 0 to 12 and reflect recent, long-term learning, with higher scores indicating better learning.
Change in Verbal Learning Test Scores
Potential LIFUP-related changes in memory will be assessed via the Rey Auditory Verbal Learning Test (RAVLT) neuropsychological assessment. The RAVLT involves providing participants with 15 unrelated words and asking them to recall the word list. There are 5 trials designed to determine short-term memory and then a 20 minute delay to assess long-term memory. The total words correct in both the short- and long-term trials are used as outcome measures.
Post-hoc biomarker analysis of APOE-4 status as a predictor of tFUS efficacy
Biomarker post hoc analysis will determine the degree to which blood based biomarkers predict the level of effectiveness of tFUS. Samples are collected before LIFUP is administered.
Post-hoc biomarker analysis of plasma AB42/40 ratio as a predictor of tFUS efficacy
Biomarker post hoc analysis will determine the degree to which blood based biomarkers predict the level of effectiveness of tFUS. Samples are collected before LIFUP is administered. An Aβ42/40 ratio \<0.160 suggests a higher-than-normal risk of having of AD and is warranted to support a diagnosis of AD (West et al 2021).
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University of California, Los Angeles
Lead sponsor
National Institute on Aging (NIA)
Collaborator
