tFUS for Memory in mNCD and Healthy Adults

Personalized Transcranial Focused Ultrasound for Mild Neurocognitive Disorder and Healthy Aging

Dementia is an ongoing and growing public health crisis in the US and worldwide. The purpose of this study is to examine a form of noninvasive brain stimulation called transcranial focused ultrasound (tFUS) to the hippocampus with the goal of improving memory.

Study Overview

• Status: Enrolling by invitation
• Conditions: Healthy Aging; Mild Neurocognitive Disorder
• Intervention / Treatment: Device: Transcranial Focused Ultrasound

Detailed Description

Dementia is an ongoing and growing public health crisis in the US and worldwide. Currently, there are an estimated 6.2 million Americans living with Alzheimer's Disease (AD) the most common form of dementia accounting for roughly 75% of cases. With a growing aging population, this number is estimated to be 13.8 million in the US and 152.8 million people worldwide by 2050 with a 14% lifetime prevalence. It is difficult to treat AD, making it critical to intervene as early as possible. Mild neurocognitive disorder (mNCD) is an early stage of memory and cognitive ability loss that is more severe than normal cognitive decline due to aging. Each year, approximately 15% of people with mNCD develop dementia, making it a critical juncture where intervention could be particularly impactful. Previous research has utilized a novel technique, called transcranial focused ultrasound (tFUS), to change brain function and has measured changes to brain activity through electroencephalography (EEG) using scalp electrodes. This study will apply tFUS to the hippocampus to examine the effects on memory in healthy adults in mNCD.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Healthy Older Adults

• Age 50-85
• English as a first/primary language
• Capacity to consent
• No Diagnosis of mNCD or dementia

Exclusion Criteria for Healthy Older Adults

• Current substance use disorder, bipolar disorder, or schizophrenia spectrum or other psychotic diagnosis
• Daily/weekly anticholinergic or sedative use. Stimulants may be used pending investigator review. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen for 4 weeks prior to enrollment
• History of significant or unstable conditions that may impact cognition, such as significant cardiac, cerebrovascular, or metabolic disease, developmental disorder, or other neurologic disease (e.g., moderate to severe TBI, seizures)
• MRI or tFUS contraindications (e.g., metal implants, claustrophobia, conditions or treatments that lower seizure threshold, taking medications that have short half-lives)
• Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days

Inclusion Criteria for mNCD

• Age 50-85
• English as a first/primary language
• Diagnosed with mNCD by a healthcare provider within the past 2 years per NIA-AA or DSM-5 criteria
• Has ≥ 2 impaired scores within one cognitive domain OR ≥ 1 impaired score in ≥ 3 domains, where impaired score is defined as ≤ 16th percentile using demographically-corrected norms
• Must have a co-participant (e.g., spouse, adult child, relative, sibling, cohabitor, friend, or caregiver) with at least weekly in-person contact with the participant

Exclusion Criteria for mNCD

• Prior diagnosis of dementia or major neurocognitive disorder per NIA-AA or DSM-5 criteria, and telephone interview for cognitive status (TICS) score ≤ 22
• Current substance use disorder, bipolar disorder, or schizophrenia spectrum or other psychotic diagnosis
• Daily/weekly anticholinergic or sedative use. Stimulants may be used pending investigator review. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen for 4 weeks prior to enrollment
• History of significant or unstable conditions that may impact cognition, such as significant cardiac, cerebrovascular, or metabolic disease, developmental disorder, or other neurologic disease (e.g., moderate to severe TBI, seizures)
• MRI or tFUS contraindications (e.g., metal implants, claustrophobia, conditions or treatments than lower seizure threshold, taking medications that have short half-lives)
• Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Focused Ultrasound to Location A; Focused Ultrasound will be administered to location A as condition 1. Stimulation will last 1-10 minutes	Device: Transcranial Focused Ultrasound; Using MRI-guided targeting, we will administer focused ultrasound to one of the 4 brain locations
Experimental: Focused Ultrasound to Location B; Focused Ultrasound will be administered to location B as condition 2. Stimulation will last 1-10 minutes	Device: Transcranial Focused Ultrasound; Using MRI-guided targeting, we will administer focused ultrasound to one of the 4 brain locations
Experimental: Focused Ultrasound to Location C; Focused Ultrasound will be administered to location C as condition 3. Stimulation will last 1-10 minutes	Device: Transcranial Focused Ultrasound; Using MRI-guided targeting, we will administer focused ultrasound to one of the 4 brain locations
Sham Comparator: Focused Ultrasound to Location D; Focused Ultrasound will be administered to location D as condition 4. Stimulation will last 1-10 minutes	Device: Transcranial Focused Ultrasound; Using MRI-guided targeting, we will administer focused ultrasound to one of the 4 brain locations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Face Name Associative Memory Task (Episodic Memory) effects	Determine the within-subject effects of tFUS on episodic memory (Face Name Associative Memory Task)	Pre- to post-stimulation (within approximately a 1 hour time period)
Electroencephalography (EEG) effects	Determine the effects of tFUS on EEG recorded from scalp electrodes from pre- to post-stimulation. The investigators will evaluate broadband effects ranging from delta (1-4Hz) to beta (25-40Hz) ranges.	Pre- to post-stimulation (within approximately a 1 hour time period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of tFUS (self report 0-10 scale)	Ratings on a scale of 0-10 gauging the side effects of stimulation on headache, pain, and other potential side effects.	Pre- to post-stimulation (within approximately a 1 hour time period)

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Center of Neuromodulation for Rehabilitation
• Investigators: Principal Investigator: Kevin Caulfield, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 11, 2024
• First Submitted That Met QC Criteria: December 4, 2024
• First Posted (Actual): December 5, 2024

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Memory; Brain stimulation; Mild neurocognitive disorder
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders
• Other Study ID Numbers: Pro00135826

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes