Transcranial Alternating Current Stimulation for the Improvement of Episodic Memory in Healthy Older Adults

March 8, 2024 updated by: Universidade Católica Portuguesa

Memory complaints are a common symptom among Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer disease. Indeed, episodic memory and Alzheimer disease are highly sensitive to aging. Many brain areas become active when we remember an event from the past. The precuneus, part of the posterior system of default mode network, has been identified as a central node of episodic memory retrieval and a central node in various psychiatric and neurological disorders, such as Alzheimer disease. Age-related changes have been consistently found in the default mode network connectivity, occurring within its posterior areas and with the reduction of connectivity between anterior and posterior subnetwork. It has also been found that aging is associated with decreased functional connectivity in the precuneus and posterior cingulate of the default mode network. Furthermore, γ-Aminobutyric acid (GABA), which plays an essential role in regulating brain activity and modulating the default mode network, shows a decrease throughout the normal course of aging, in Mild Cognitive Impairment and Alzheimer disease. It was also verified a link between cognitive decline and the dysfunction of the inhibitory activity of GABAergic interneurons, particularly parvalbumin-positive interneurons, that play a role in control local circuitry, brain networks and memory processing. Parvalbumin interneurons are the fast-spiking interneurons that generate and maintain gamma frequency. Gamma band has been associated with the encoding and retrieval of episodic memory. Impairments of gamma oscillations have been observed in healthy aging, Mild Cognitive Impairment and Alzheimer disease.

By identifying these functional connectivity changes, non-invasive neuromodulation techniques may offer a new strategy for improving cognitive functions. Transcranial Alternating Current Stimulation (tACS) is a form of non-invasive brain stimulation that modulates cortical activity by applying weak, oscillating electrical currents to the cortex via two or more scalp electrodes. By using alternating currents, it is possible to simulate the rhythmic pattern of electrophysiological activity of the brain. tACS can interact with neural firing at behaviorally relevant frequencies linked to memory.

In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether stimulation with gamma tACS on the precuneus can improve episodic memory in healthy older adults.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Memory complaints are a common symptom among Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer disease. Indeed, episodic memory and Alzheimer disease are highly sensitive to aging. Many brain areas become active when we remember an event from the past. The precuneus, part of the posterior system of default mode network, has been identified as a central node of episodic memory retrieval and a central node in various psychiatric and neurological disorders, such as Alzheimer disease. Age-related changes have been consistently found in the default mode network connectivity, occurring within its posterior areas and with the reduction of connectivity between anterior and posterior subnetwork. It has also been found that aging is associated with decreased functional connectivity in the precuneus and posterior cingulate of the default mode network. Furthermore, γ-Aminobutyric acid (GABA), which plays an essential role in regulating brain activity and modulating the default mode network, shows a decrease throughout the normal course of aging, in Mild Cognitive Impairment and Alzheimer disease. It was also verified a link between cognitive decline and the dysfunction of the inhibitory activity of GABAergic interneurons, particularly parvalbumin-positive interneurons, that play a role in control local circuitry, brain networks and memory processing. Parvalbumin interneurons are the fast-spiking interneurons that generate and maintain gamma frequency. Gamma band has been associated with the encoding and retrieval of episodic memory. Impairments of gamma oscillations have been observed in healthy aging, Mild Cognitive Impairment and Alzheimer disease.

By identifying these functional connectivity changes, non-invasive neuromodulation techniques may offer a new strategy for improving cognitive functions. Transcranial Alternating Current Stimulation (tACS) is a form of non-invasive brain stimulation that modulates cortical activity by applying weak, oscillating electrical currents to the cortex via two or more scalp electrodes. By using alternating currents, it is possible to simulate the rhythmic pattern of electrophysiological activity of the brain. tACS can interact with neural firing at behaviorally relevant frequencies linked to memory.

In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether stimulation with gamma tACS on the precuneus can improve episodic memory in healthy older adults.

Participants will be randomized into two groups in a 1:1 ratio, and the order of administration of either intervention (i.e., gamma-tACS or sham) will be counterbalanced across all participants. Stimulation will be inverted (crossover phase) after 1 week (wash-out). Participants will be evaluated with neuropsychological tests (AVLT and FNMT) and neurophysiological measures of functional connectivity (rs EEG).

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Portugal
      • Lisbon, Portugal
        • Filipa Ribeiro
        • Contact:
        • Principal Investigator:
          • Joana Macedo, MSc
        • Principal Investigator:
          • Filipa Ribeiro, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Older adults aged 65 or over;
  • Normal general cognition: score within the normative values for the Portuguese population in the Addenbrooke's Cognitive Examination

Exclusion Criteria:

  • Neurological disorders (stroke, tumours, significant head trauma, and epilepsy), psychiatric conditions (such as autism, schizophrenia, depression), or uncontrolled medical illness (hypertension, metabolic, endocrine, toxic, and infectious diseases) able to interfere with cognition;
  • Sensory deficits likely to interfere with neuropsychological assessment;
  • Impairment in activities of daily living;
  • Chronic alcohol or drug abuse;
  • Non-native Portuguese speakers;
  • Metal implants on the head or implanted electronic devices.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: real tACS
5 sessions of gamma tACS (40 Hz) at 2 mA over the Precuneus
Device: Gamma tACS (40 Hz) over the precuneus
5 sessions of gamma tACS (40 Hz) over the precuneus
Sham Comparator: Placebo Comparator: sham tACS
5 sessions of sham over the Precuneus
Device: Sham tACS over the precuneus
5 sessions of sham tACS over the precuneus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in immediate and delayed free recall Auditory Verbal Learning Test scores
Time Frame: Baseline (immediately before the stimulation protocol/on the first session/day 1) and post stimulation (after 5 sessions of 5 consecutive days of gamma tACS/sham/day 5). After one week, measures will be repeated in the crossover phase day 12 and 17.
Auditory Verbal Learning Test is a list-learning paradigm, and consists of five consecutive immediate free recall trials, a delayed free recall trial (after 30 minutes of the fifth immediate free recall trial), and a delayed recognition trial. Different lists will be used during pre- and post-stimulation to avoid learning effects.
Baseline (immediately before the stimulation protocol/on the first session/day 1) and post stimulation (after 5 sessions of 5 consecutive days of gamma tACS/sham/day 5). After one week, measures will be repeated in the crossover phase day 12 and 17.
Changes in immediate free recall and delayed recognition Face-Name Memory Test scores
Time Frame: During the first session/day 1 of intervention of gamma tACS/sham and during the first session on the crossover-phase/day12
Face-Name Memory Test requires learning 20 unfamiliar face-name pairs and include a training, initial learning phase (learning 1 and 2), immediate recall and after 30 minutes a delayed recall, facial recognition, and a multiple-choice recognition trial. During learning phase (1 and 2) participants will underwent two exposures to all 20 face and name. It is shown a face on a grey background with a fictional first name printed in black underneath the face, forming a face-name pair; the participants must say whether the photograph they see is of a man or a woman, read the name below out loud and try to learn each face-name pair. Following each exposure, they were asked for name associated with each face. After a 30-minute delay they were asked to identify the previously learned face from three pictures, asked for name associated with each face, and asked to select the name associated with the face among four proper names
During the first session/day 1 of intervention of gamma tACS/sham and during the first session on the crossover-phase/day12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in functional connectivity
Time Frame: Baseline (immediately before the stimulation protocol/on the first session/day 1) and post stimulation (after 5 sessions of 5 consecutive days of gamma tACS/sham/day 5). After one week, measures will be repeated in the crossover phase day 12 and 17.
By using resting state electroencephalogram the investigators will evaluate the effects of gamma tACS in functional connectivity between precuneus and hippocampus
Baseline (immediately before the stimulation protocol/on the first session/day 1) and post stimulation (after 5 sessions of 5 consecutive days of gamma tACS/sham/day 5). After one week, measures will be repeated in the crossover phase day 12 and 17.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidade Católica Portuguesa

Collaborators

Clínica NeuroVida (Portugal)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

October 31, 2024

Study Completion (Estimated)

October 31, 2024

Study Registration Dates

First Submitted

January 27, 2024

First Submitted That Met QC Criteria

February 21, 2024

First Posted (Actual)

February 29, 2024

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 8, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • Project number 144

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All data, including outcome measure results, study protocol and statistical analysis plan, will be shared upon reasonable request

IPD Sharing Time Frame

Data will be shared after the study completion indefinitely.

IPD Sharing Access Criteria

Reasonable request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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