Alzheimer DiseaseMementoNCT06202872
Memory Enhancement Using Transcranial Alternating Current Stimulation
A study testing Gamma (40 Hz) tACS at the precuneus region in people with Alzheimer Disease and Mild Cognitive Impairment, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment
- What is being tested?
- Gamma (40 Hz) tACS at the precuneus region
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteNetherlands
- Study dates
- 15 Nov 2024to 7 May 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Amsterdam UMC, The Netherlands
Amsterdam, North Holland, 1081HV
About this study
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
- Being tested
- Gamma (40 Hz) tACS at the precuneus region, Sham tACS at the precuneus region
- Keywords
- Alzheimer's disease, Transcranial alternating current stimulation, Episodic memory, Magnetoencephalography
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gamma (40 Hz) tACS at the precuneus regionDevice
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)
Sham tACS at the precuneus regionDevice
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)
| Study group | Role | What they receive |
|---|---|---|
| Active tACS | Experimental | Gamma (40 Hz) tACS at the precuneus region Receives: Device: Gamma (40 Hz) tACS at the precuneus region |
| Sham tACS | Sham comparator | Sham tACS at the precuneus region Receives: Device: Sham tACS at the precuneus region |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Immediately before and after intervention
Secondary outcomes (7)
Change in spectral source space resting-state MEG (relative power)
Change in relative power will be used, expecting an increase in relative power in higher alpha, beta and gamma bands and decrease in relative power in theta band after active but not sham tACS.
Measured: Immediately before and after intervention
Change in spectral source space resting-state MEG (posterior peak frequency)
Change in posterior peak frequency will be used, expecting an increase in posterior peak frequency after active but not sham tACS.
Measured: Immediately before and after intervention
Change in functional connectivity source space resting-state MEG (AEC-c)
Change in corrected amplitude envelope correlation (AEC-c) will be used, expecting an increase in AEC-c in higher alpha, beta and gamma bands after active but not sham tACS.
Measured: Immediately before and after intervention
Change in functional connectivity source space resting-state MEG (PLI)
Change in phase lag index (PLI) will be used, expecting a decrease in PLI in theta band after active but not sham tACS.
Measured: Immediately before and after intervention
Change in source space resting-state MEG network structure (MST variables)
Change in graph theory parameters will be used as a measure of global network structure. Restoration of overall network configuration (expressed by shift of multiple Minimum spanning tree (MST) parameters towards healthy state, e.g. stronger hierarchy) after active but not sham tACS is expected.
Measured: Immediately before and after intervention
Change in source space resting-state MEG network structure (clustering coefficient and path length)
Change in graph theory parameters will be used as a measure of global network structure. Preserved small-world configuration (shift of small world index (clustering coefficient/path length) towards less random topology) after active but not sham tACS is expected.
Measured: Immediately before and after intervention
Change in source space resting-state MEG network structure (modulatory index, degree and eigenvector centrality)
Change in graph theory parameters will be used as a measure of mesoscale network structure (modularory measures) and nodal characteristics (degree and eigenvector centrality). Restoration of hub disruption (stronger modularity index, increase in degree and eigenvector centrality) of precuneus-posterior cingulate and medial temporal lobe after active but not sham tACS is expected.
Measured: Immediately before and after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2024
- Study start15 Nov 2024
- Primary completion28 Apr 2026
- Study completion7 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, sham-controlled, crossover trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Willem de Haan, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Willem de Haan, dr., Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06202872
- Sponsor's protocol ID
- 20212222
- Acronym
- Memento
- Status last verified
- May 2026
- First submitted
- 22 Dec 2023
- Last updated
- 2 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The individual participant data will be made available upon reasonable request to the corresponding author in consultation with the data protection officer
Publications
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.
PubMed 33762220Benussi 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.
PubMed 35607946Grover 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.
PubMed 37224229Iaccarino 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.
PubMed 27929004Maestu 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.
PubMed 34029743Palop 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.
PubMed 27829687
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Memory Enhancement Using Transcranial Alternating Current Stimulation
- ClinicalTrials.gov ID
- NCT06202872
- Acronym / sponsor ID
- Memento / 20212222
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Keywords
- Alzheimer's disease, Transcranial alternating current stimulation, Episodic memory, Magnetoencephalography
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 15 Nov 2024 (actual)
- Primary completion
- 28 Apr 2026 (actual)
- Study completion
- 7 May 2026 (actual)
- First posted
- 12 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, sham-controlled, crossover trial
| Arm | Type | Receives |
|---|---|---|
| Active tACS | Experimental | Device: Gamma (40 Hz) tACS at the precuneus regionGamma (40 Hz) tACS at the precuneus region |
| Sham tACS | Sham comparator | Device: Sham tACS at the precuneus regionSham tACS at the precuneus region |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gamma (40 Hz) tACS at the precuneus region40 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) | Device | Active tACS |
| Sham tACS at the precuneus regionSham 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) | Device | Sham tACS |
Primary outcome
Change in Rey Auditory Verbal Learning test scores
Time frame: Immediately before and after intervention
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.
Change in Face-Name Association Task scores
Time frame: Immediately before and after intervention
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.
7 secondary outcomes
Change in spectral source space resting-state MEG (relative power)
Time frame: Immediately before and after intervention
Change in spectral source space resting-state MEG (posterior peak frequency)
Time frame: Immediately before and after intervention
Change in functional connectivity source space resting-state MEG (AEC-c)
Time frame: Immediately before and after intervention
Change in functional connectivity source space resting-state MEG (PLI)
Time frame: Immediately before and after intervention
Change in source space resting-state MEG network structure (MST variables)
Time frame: Immediately before and after intervention
Change in source space resting-state MEG network structure (clustering coefficient and path length)
Time frame: Immediately before and after intervention
Change in source space resting-state MEG network structure (modulatory index, degree and eigenvector centrality)
Time frame: Immediately before and after intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2026.
- Background: PubMed 33762220Benussi 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.
- Background: PubMed 35607946Benussi 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.
- Background: PubMed 37224229Grover 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.
- Background: PubMed 27929004Iaccarino 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.
- Background: PubMed 34029743Maestu 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.
- Background: PubMed 27829687Palop 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.
- Individual participant dataSharing planned: Yes. The individual participant data will be made available upon reasonable request to the corresponding author in consultation with the data protection officer
Related trials for Alzheimer Disease
Not yet recruitingPhase 1
A Study to Learn How Different Amounts of the Study Medicine Called PF-08161842 Are Tolerated and Act in the Body in Healthy and Older Adults
Alzheimer Disease
Active, not recruiting
Emergency Preparedness for Caregivers of Persons With Dementia: Disaster PrepWise
Caregiver Resilience and Stress
Active, not recruitingObservational study
A Community-Based Screening Program to Identify Participants at High Risk for Amyloid Pathology
Alzheimer's Disease
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Amyloid PET Imaging in the Baltimore Longitudinal Study of Aging
Aging
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Willem de Haan, dr. principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Gamma (40 Hz) tACS at the precuneus region in people with Alzheimer Disease and Mild Cognitive Impairment, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Rey Auditory Verbal Learning test scores (time frame: Immediately before and after intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06202872, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.