Feasibility of Gamma Transcranial Alternating Current Stimulation to Reduce Beta-amyloid Load and Improve Memory

This project assessed the feasibility of transcranial alternating current stimulation in the gamma band to lower beta-amyloid load and improve memory performance.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Device: Transcranial alternating current stimulation

Detailed Description

Thirteen individuals with aMCI received eight 60-minute sessions of 40-Hz (gamma) transcranial alternating current stimulation (tACS) in a single-arm design. Outcome measures were assessed pre- and post-intervention.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• English speaking
• Grade 12 or more education
• Normal or corrected to normal vision and hearing
• Ability to complete cognitive tasks
• Ability to cooperate and comply with all study procedures
• Ability to tolerate tACS
• Self-reported memory complaint
• Diagnosed with mild cognitive impairment
• Amyloid positive

Exclusion Criteria:

• Neurological or psychiatric disorders other than mild cognitive impairment
• Receiving investigational medications or have participated in a trial with investigational medications within last 30 days
• Family history of epilepsy
• Implanted electronic devices (e.g., pacemaker)
• Prior head trauma
• Pregnant
• IQ < 80
• Taking cholinesterase inhibitory, memantine, or psychotropic medication
• Taking anti-depressants or anti-anxiety medication
• Color blind
• Substance abuse
• Glaucoma
• Macular degeneration
• Amblyopia (lazy eye)
• Strabismus (crossed eyes)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gamma Stimulation Group; This group will receive gamma stimulation	Device: Transcranial alternating current stimulation; Transcranial alternating current stimulation (tACS) will be applied at 40 Hz (gamma band) during eight sessions over the course of a month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects	Side effects were measured on a scale from 0 (not noticable) to 10 (not tolerable): headache, neck pain, scalp pain, tingling, itching, burning sensation, increased sleepiness, trouble concentrating, acute mood change, and phosphenes. Average rating across all measures reported as indicator of side effects.	Average of all post-tACS sessions, up to 1 month
Drop Out	Drop out rate will be assessed as the number of participants who withdraw or are withdrawn from the study.	post-tACS, up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta Amyloid Load Change	Change in plasma-based beta amyloid (AB) load was assessed as the AB42/40 ratio, calculated as post minus pre AB42/40 ratio. Greater increase is better.	pre-tACS (baseline) and post-tACS (1 month)
Memory: Recall Change	Episodic memory was assessed pre and post intervention as the number of words correct during the short delay free recall portion of the California Verbal Learning Test. Change was assessed as post minus pre. Greater increase is better.	pre-tACS (baseline), post-tACS (after one month of treatment)
Memory: Paired Associates Change	Episodic memory was assessed pre and post intervention from memory accuracy for a paired associates task for visual objects. Change was assessed post minus pre. Greater increase is better.	pre-tACS (baseline), post-tACS (after one month of treatment)
Memory: Fluency Change	Episodic memory fluency was assessed pre and post intervention from performance on the FAS task. Unit of measurement is the number of words names starting with the letter f, a, or s. Change was calculated as post minus pre. Greater increase is better.	pre-tACS (baseline), post-tACS (after one month of treatment)
Change in Tau	Plasma tau levels was assessed pre and post intervention. Change was calculated as post minus pre. Greater decrease is better.	pre-tACS (baseline), post-tACS (after one month of treatment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting state functional connectivity (RSFC)	RSFC will be assessed as a predictor of tACS effects. Modularity will be calculated and used in a regression model.	pre-tACS
Change in Resting state functional connectivity (RSFC)	Change in RSFC will be assessed pre and post intervention.	pre-tACS (baseline), post-tACS (after one month of treatment)
Magnetic resonance spectroscopy (MRS)	MRS will be assessed as a predictor of tACS effects. The ratio of excitatory (GLX+) to inhibitory (GABA) neurotransmitters will be used in a regression model.	pre-tACS
Change in Magnetic resonance spectroscopy (MRS)	Change in MRS will be assessed pre and post intervention.	pre-tACS (baseline), post-tACS (after one month of treatment)
Modeled electric field (EF)	EF will be assessed as a predictor of tACS effects. EF magnitude will be calculated from T1 and T2 images, and used in a regression model.	pre-tACS
Instrumental activities of daily living (IADL)	Change in IADL will be assessed pre and post intervention.	pre-tACS (baseline), post-tACS (after one month of treatment)
Neurofilament Light	Change in blood neurofilament light levels will be assessed pre and post intervention.	pre-tACS (baseline), post-tACS (after one month of treatment)
Neurogranin	Change in blood neurogranin levels will be assessed pre and post intervention.	pre-tACS (baseline), post-tACS (after one month of treatment)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Theodore Zanto, Ph.D., University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): May 31, 2022

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 30, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 131887a; R21AG060335 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The dataset includes self-reported information, behavioral and electrophysiological data. The final dataset will be stripped of identifiers prior to release for sharing, thereby anonymizing the data. We will make the anonymized data available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to attempt to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed. This will be in accordance with human subject regulations.
• IPD Sharing Time Frame: The data will be available after the results have been determined and the study researchers are unblinded. The data will be available indefinitely upon request.
• IPD Sharing Access Criteria: Contact PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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.: No