Memory Enhancement Using Transcranial Alternating Current Stimulation

NCT06202872 | Recruiting DMC

• 1 other identifier: 20212222
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The 32 million Alzheimer's disease (AD) and 69 million prodromal AD patients worldwide contribute to a large economic burden. Effective and safe therapies that slow or prevent the progression from mild cognitive impairment (MCI) to AD are therefore of high priority. Transcranial alternating current stimulation (tACS) is a safe and patient-friendly non-invasive brain stimulation technique that serves as a potential candidate for reducing and/or slowing cognitive impairment. Application of tACS in the gamma frequency range, specifically around 40 Hz, has been studied in patients with AD and MCI due to AD. In these patients, a single session of 40 Hz tACS at the precuneus showed to improve episodic memory and to increase gamma power, as measured with electroencephalography. These findings will be replicated in the current study in patients with MCI due to AD, using magnetoencephalography (MEG) recorded before, during and after tACS. In this way, brain activity and network changes that underlie this improvement in episodic memory can be studied with greater temporal and spatial detail.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Keywords

Alzheimer's disease; Transcranial alternating current stimulation; Episodic memory; Magnetoencephalography

Outcome Measures

Primary Outcomes (2)

• Change in Rey Auditory Verbal Learning test scores

  The Rey Auditory Verbal Learning (RAVL) test evaluates verbal episodic memory and is designed as a list-learning paradigm in which the subject hears a list of 15 nouns. The participant is asked to recall as many words from the list as possible after each of 5 repetitions of free-recall (total recall), and 15 minutes after an interference trial (long delayed recall). Scores range from 0 to 75 (total recall) and 0 to 15 (long delayed recall), with higher scores meaning a better outcome. An increase in RAVL test (total and long delayed recall) after active but not sham tACS is expected.

  Immediately before and after intervention

• Change in Face-Name Association Task scores

  The Face-Name Association Task assesses associative episodic memory and is a computer paradigm consisting of an encoding and a retrieval phase of face-name pairs. During the encoding phase, participants are instructed to remember a set of 12 faces and names they are paired. In two additional learning trials, participants are shown the previously learned faces and are asked to recall the correct name associated with each face (inital recognition). This recall of the correct name associated with a learned face is repeated 5 minutes after the learning trials during the retrieval phase (associative recognition). Scores range from 0 to 24 (inital recognition) and 0 to 12 (associative recognition), with higher scores meaning a better outcome. An increase in FNAT score (initial and associative recognition) after active but not sham tACS is expected.

  Immediately before and after intervention

Secondary Outcomes (7)

• Change in spectral source space resting-state MEG (relative power)

  Immediately before and after intervention

• Change in spectral source space resting-state MEG (posterior peak frequency)

  Immediately before and after intervention

• Change in functional connectivity source space resting-state MEG (AEC-c)

  Immediately before and after intervention

• Change in functional connectivity source space resting-state MEG (PLI)

  Immediately before and after intervention

• Change in source space resting-state MEG network structure (MST variables)

  Immediately before and after intervention

Study Arms (2)

Active tACS

EXPERIMENTAL

Gamma (40 Hz) tACS at the precuneus region

Device: Gamma (40 Hz) tACS at the precuneus region

Sham tACS

SHAM COMPARATOR

Sham tACS at the precuneus region

Device: Sham tACS at the precuneus region

Interventions

Gamma (40 Hz) tACS at the precuneus region DEVICE

40 Hz tACS applied at a current of 3.2 milliampere peak-to-peak using a NuroStym transcranial electrical stimulation (tES) system of NeuroDevice for four times 12 minutes (48 minutes in total) at the Pz (according to the 10-20 international EEG coordinates)

Active tACS

Sham tACS at the precuneus region DEVICE

Sham tACS applied with no effective stimulation between the ramp-up and ramp-down of the current using a NuroStym tES system of NeuroDevice for four times 12 minutes (48 minutes in total) at the Pz (according to the 10-20 international EEG coordinates)

Sham tACS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recent (not more than 6 months ago) amnestic MCI diagnosis, which consensus is obtained in a multidisciplinary meeting after an extended multidisciplinary test battery at the memory clinic, including confirmation of AD pathology with cerebrospinal fluid biomarkers: abnormal p-tau/Aβ42 ratio of \> 0.023

You may not qualify if:

• Suffering from serious neurological, psychiatric or somatic comorbidity
• Suffering from epileptic seizures or severe claustrophobia
• Intensive use of psychoactive medication
• Having a cardiac pacemaker, internal cardiac defibrillator or other intracorporeal device that interferes with MEG recordings

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Amsterdam UMC, The Netherlands

Amsterdam, North Holland, 1081HV, Netherlands

RECRUITING

Related Publications (6)

• Benussi A, Cantoni V, Cotelli MS, Cotelli M, Brattini C, Datta A, Thomas C, Santarnecchi E, Pascual-Leone A, Borroni B. Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 2021 May-Jun;14(3):531-540. doi: 10.1016/j.brs.2021.03.007. Epub 2021 Mar 21.

  PMID: 33762220 BACKGROUND

• Benussi A, Cantoni V, Grassi M, Brechet L, Michel CM, Datta A, Thomas C, Gazzina S, Cotelli MS, Bianchi M, Premi E, Gadola Y, Cotelli M, Pengo M, Perrone F, Scolaro M, Archetti S, Solje E, Padovani A, Pascual-Leone A, Borroni B. Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease. Ann Neurol. 2022 Aug;92(2):322-334. doi: 10.1002/ana.26411. Epub 2022 Jun 6.

  PMID: 35607946 BACKGROUND

• Grover S, Fayzullina R, Bullard BM, Levina V, Reinhart RMG. A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. Sci Transl Med. 2023 May 24;15(697):eabo2044. doi: 10.1126/scitranslmed.abo2044. Epub 2023 May 24.

  PMID: 37224229 BACKGROUND

• Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587.

  PMID: 27929004 BACKGROUND

• Maestu F, de Haan W, Busche MA, DeFelipe J. Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology. Ageing Res Rev. 2021 Aug;69:101372. doi: 10.1016/j.arr.2021.101372. Epub 2021 May 21.

  PMID: 34029743 BACKGROUND

• Palop JJ, Mucke L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat Rev Neurosci. 2016 Dec;17(12):777-792. doi: 10.1038/nrn.2016.141. Epub 2016 Nov 10.

  PMID: 27829687 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Willem de Haan, dr.

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Willem de Haan, dr.

CONTACT

(0)20 444 0722; w.dehaan@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized, sham-controlled, crossover trial

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: January 12, 2024
• Study Start: November 15, 2024
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: December 20, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be shared after the study completion indefinitely
• Access Criteria: Upon reasonable request

Locations

NL (1)