The Effect of TPS on Cognitive Functions in Older Adults With MCI

The Effect of Transcranial Pulse Stimulation on Cognitive Functions in Older Adults With Mild Cognitive Impairment: A Randomized Controlled Trial

The goal of this randomized controlled trial is to learn if Transcranial Pulse Stimulation (TPS) can improve cognitive functions in older adults with mild cognitive impairment (MCI). The study will also assess the safety of TPS. The main questions it aims to answer is:

Does TPS improve cognitive functions such as global cognition, attention, memory, and executive function?

Researchers will compare TPS to a sham control to evaluate the efficacy and safety of TPS in improving cognitive functions in older adults with MCI.

Participants will:

Be randomly assigned to receive either TPS or a sham intervention Undergo 6 sessions of TPS or sham intervention over a 2-week period Visit the clinic for cognitive assessments at 4 different time points (baseline, immediately post-intervention, 1-month follow-up, and 3-month follow-up) Complete questionnaires and undergo standardized neurocognitive tests, and/or MRI scans, and/or EEG assessments

The study aims to provide insights into the potential therapeutic role of TPS in enhancing cognitive functions among older adults with mild cognitive impairment.

Study Overview

• Status: Enrolling by invitation
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Behavioral: transcranial pulse stimulation; Behavioral: Sham TMS

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Department of Psychology

Participation Criteria

Eligibility Criteria

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

Description

Eligibility Criteria

Inclusion Criteria:

Community-dwelling older adults aged 55 and above

Diagnosed with Mild Cognitive Impairment (MCI), classified based on:

Subjective reporting of memory deficits A score of 19-24 on the Hong Kong version of the Montreal Cognitive Assessment (HK-MoCA) A score greater than 2 standard deviations on the Lawton Instrumental Activities of Daily Living (IADL) scale A score of 1 point or less on the AD8 questionnaire Right-handedness Ability to cooperate with assessment and intervention, without significant communicative impairments Absence of depression or anxiety, scoring less than 8 on both the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A)

Exclusion Criteria:

Current or history of dementia or other psychiatric diseases Score greater than or equal to 5 on the Hachinski Ischemic Scale (HIS) for identifying possible vascular-related causes Current or history of alcohol or drug abuse On medication within the last 2 weeks that may affect cognitive functions Report having any present neurological or psychiatric condition besides MCI Report having hemophilia, other blood clotting disorders, or medication that may cause these conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm	Behavioral: transcranial pulse stimulation; Participants in the experimental arm will receive six sessions of Transcranial Pulse Stimulation (TPS) over a two-week period, using the NEUROLITH® TPS system (Storz Medical AG, Switzerland). Each session will involve delivering 6,000 ultrasound pulses at an energy level of 0.2-0.25 mJ/mm² and a frequency of 4-5 Hz, targeting specified brain regions based on MRI navigation.
Sham Comparator: Sham Control Arm	Behavioral: Sham TMS; Participants in the sham control group will undergo six sessions over a two-week period, utilizing the same NEUROLITH® TPS system (Storz Medical AG, Switzerland) as used in the experimental group. The key difference lies in the standoff device attached to the handpiece: while the experimental arm uses a standoff filled with silicone oil to transmit ultrasound pulses, the sham group's standoff is filled with air. This design ensures that the sham device replicates the appearance, feel, and sound of the active treatment without transmitting any therapeutic pulses, effectively maintaining the blinding aspect of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Global Cognitive Function	Change in global cognitive function scores from baseline, as measured by the Hong Kong version of the Montreal Cognitive Assessment (HK-MoCA). The HK-MoCA assesses various cognitive domains, including attention, memory, language, visuospatial skills, and executive functions. Scores on the HK-MoCA range from 0 to 30, with higher scores indicating better cognitive function.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Auditory Attention	Change in auditory attention scores from baseline, as measured by the Auditory Attention Span (AAS) test. This test assesses participants' ability to maintain focus on auditory stimuli and recall sequences of numbers or words. Higher scores indicate better auditory attention performance.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Visual Attention	Change in visual attention scores from baseline, as measured by the Visual Attention Span (VAS) test. The VAS test assesses the ability to maintain and recall visual stimuli. Higher scores reflect better visual attention.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Sustained Attention	Change in sustained attention scores from baseline, as measured by the Continuous Performance Test (CPT). This test evaluates sustained attention and response control, with higher scores indicating improved sustained attention over time.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Visual-Spatial Judgment	Change in visual-spatial judgment scores from baseline, as measured by the Vision Space Judgment (VSJ) test. This test evaluates the ability to judge spatial relationships between objects, with higher scores indicating improved visual-spatial judgment.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Working Memory	Change in working memory scores from baseline, as measured by the Math Problems (MP) task. This test evaluates the ability to store and manipulate information related to calculations in working memory. Higher scores indicate better working memory performance.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Working Memory (Math)	Change in working memory scores from baseline, as measured by the Math Problems (MP) task. This test evaluates the ability to store and manipulate information related to calculations in working memory. Higher scores indicate better working memory performance.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Working Memory (General)	Change in working memory scores from baseline, as measured by the Working Memory (WM) task. This test evaluates participants' ability to retain and manipulate verbal and non-verbal information. Higher scores indicate better working memory performance.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Verbal Memory	Change in verbal memory scores from baseline, as measured by the Verbal Memory List Learning (VMLL) task. This task assesses the ability to encode, store, and retrieve verbal information. Higher scores indicate improved verbal memory.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Processing Speed	Change in processing speed scores from baseline, as measured by the Symbol Digit Modality Test (SDMT). This test assesses the speed of processing visual information and converting it into a motor response. Higher scores indicate better processing speed.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Language - Vocabulary	Change in vocabulary scores from baseline, as measured by the Receptive Vocabulary (RV) task. This test evaluates participants' understanding and recognition of spoken words. Higher scores indicate improved language and vocabulary skills.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Executive Functioning - Fluency	Change in executive functioning scores from baseline, as measured by the Figural Fluency Test (FFT). This test assesses participants' ability to generate novel responses and plan effectively. Higher scores indicate better executive functioning.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Depressive Symptoms	Change in depressive symptoms from baseline, as measured by the Hamilton Depression Rating Scale (HAM-D). Higher scores indicate more severe depressive symptoms, while lower scores indicate improvement.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Anxiety Symptoms	Change in anxiety symptoms from baseline, as measured by the Hamilton Anxiety Rating Scale (HAM-A). Higher scores indicate more severe anxiety symptoms, while lower scores indicate improvement.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Instrumental Activities of Daily Living	Change in functional independence from baseline, as measured by the Hong Kong Lawton Instrumental Activities of Daily Living (IADL) Scale. Higher scores indicate greater independence in daily living activities.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up
Improvement in Quality of Life	Change in quality of life scores from baseline, as measured by the Quality of Life in Alzheimer's Disease (QoL-AD) scale. Higher scores indicate better perceived quality of life.	Baseline, immediately post-intervention, 1-month follow-up, 3-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Reactions	Monitoring of adverse reactions using a self-reported questionnaire after each TPS session. The questionnaire assesses potential side effects such as headaches, dizziness, or other discomforts.	Immediately after each TPS session

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Leung Pong Lee, MOT MPsyMed, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 9, 2024

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: PSYTPS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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