AgingNCT06563453
Implication of Cognitive Reserve in Non-pharmacological Intervention Outcomes
A study testing transcranial alternating current stimulation in people with Aging and Mild Cognitive Impairment, run by Masaryk University at 1 site in Czechia.
Trial summary
Cognitive reserve (CR) is defined as the gradual accumulation of neural resources and their adaptability (i.e., efficiency, capacity, flexibility) due to genetic and/or lifelong environmental factors that mitigate the cognitive effects of age-related processes and brain diseases. Read more about this study
- Who is it for?
- Ages 60 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging, Mild Cognitive Impairment, Dementia With Lewy Bodies
- What is being tested?
- transcranial alternating current stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- 1 siteCzechia
- Study dates
- 18 Jun 2022to 31 Dec 2024
- 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 60 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Intact cognitive performance as assessed by cognitive evaluation.
- Subjects with possible or probable mild cognitive impairment with Lewy bodies (MCI-LB).
Who cannot join
- Presence of dementia as assessed by a cognitive test battery and evaluation of daily activities.
- Any major psychiatric disorder.
- History of neurological disease affecting the central nervous system (e.g., tumor, epilepsy, stroke, etc.).
- Severe or repeated head injury.
- Non-compensated internal or oncological disease. MRI-incompatible metal in the body (e.g., pacemaker). Left-handedness.
Trial locations and contacts
1 site in 1 country.
About this study
Cognitive reserve (CR) is defined as the gradual accumulation of neural resources and their adaptability (i.e., efficiency, capacity, flexibility) due to genetic and/or lifelong environmental factors that mitigate the cognitive effects of age-related processes and brain diseases. Transcranial alternating current stimulation (tACS) can be used to entrain underlying neuronal networks, promoting firing at specific frequencies. Recent studies have demonstrated that fronto-parietal theta oscillatory activity entrainment via tACS leads to working memory enhancement in healthy subjects. However, there remains significant variability in stimulation-induced aftereffects across individuals.
Emerging literature suggests that individual differences, such as CR levels, may be crucial in predicting the benefits of treatment interventions, as they reflect available neural capacity and flexibility. A novel interventional approach is proposed to study CR, utilizing both conventional static proxies, such as premorbid intellect and educational attainment, and dynamic markers, including pupillometry, resting-state, and task-induced functional MRI. By employing cutting-edge noninvasive brain stimulation (NIBS) techniques, the study will acutely modulate network properties to examine the influence of CR on immediate cognitive and brain functional aftereffects induced by the intervention. In addition to focusing on cognitively healthy older adults, this study will, for the first time, include patients with mild cognitive impairment with Lewy bodies (MCI-LB), a prodromal stage of the second most common degenerative dementia after Alzheimer's disease.
Read the detailed description
A novel interventional approach is proposed for studying cognitive reserve (CR) using dynamic biomarkers, including:
Neuromelanin-sensitive MRI sequences to evaluate signal intensity of the locus coeruleus, Resting-state functional MRI (rs-fMRI) to evaluate network properties such as modularity and local and global efficiency, Baseline dynamic rs-fMRI to evaluate mean dwell time and number of transitions between states, and Baseline task-induced activation to evaluate engagement of "domain-specific" and "domain-general" regions during the 'offline' transfer working memory (WM) task performance, i.e., tasks solved after transcranial alternating current stimulation (tACS).
These dynamic biomarkers are used in addition to established conventional static proxies (education and premorbid intellect).
Specifically, the study aims to:
Assess which CR biomarkers and conventional CR proxies, alone or in combination, best predict the tACS-induced magnitude of cognitive enhancement of the 'online' WM task (solved while stimulated).
Evaluate the influence of CR on the recruitment of compensatory mechanisms (as assessed by task-induced fMRI and rs-fMRI) induced by tACS for solving challenging WM tasks.
Investigate how the CR level moderates the relationship between the magnitude and spatial patterns of brain flexibility changes induced by an acute tACS (as measured by pupil dilation during the online WM task performance and pre-post tACS resting-state functional connectivity changes within and between large-scale brain networks) and cognitive tACS-induced enhancement (as measured by 'online' WM task performance and changes in the 'offline' transfer task performance solved after stimulation).
- Conditions
- Aging, Mild Cognitive Impairment, Dementia With Lewy Bodies
- Being tested
- transcranial alternating current stimulation
- Medical subject headings
- Cognitive Dysfunction, Lewy Body Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial alternating current stimulationDevice
Transcranial Alternating Current Stimulation (tACS) is a tool that administers a weak alternating current (in the range of 0.1 to 4 mA), most often with a sinusoidal waveform, between electrodes placed over target areas. This can entrain the subjacent neuronal networks favouring the firing at specific frequencies of interest, in certain cases, with effects outlasting the stimulation duration up to 70 min.
| Study group | Role | What they receive |
|---|---|---|
| sham stimulation | Sham comparator | Two inactive electrodes (anodes and cathodes) - placed over Medial frontal lobe and Inferior parietal lobe. The flow of current discontinues after 20 seconds, the stimulation continues. Receives: Device: transcranial alternating current stimulation |
| frontal stimulation | Experimental | One active electrode (anode and cathode) - placed over Medial frontal lobe, one inactive electrode (anode and cathode) - placed over Inferior parietal lobe.
Current intensity - 2 (milliamperes) mA, frequency: theta 4.51 Hz, stimulation time: 20 minutes Receives: Device: transcranial alternating current stimulation |
| frontoparietal stimulation | Experimental | One active electrode (anode and cathode) - placed over Medial frontal lobe, another active electrode (anode and cathode) - placed over Inferior parietal lobe.
Current intensity - 2 mA, frequency: theta 4.51 Hz in-phase, stimulation time: 20 minutes Receives: Device: transcranial alternating current stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Accuracy of the visual 2-back and 3-back tasks in tACS conditions
The outcome measure assesses accuracy in the online working memory 2-back and 3-back tasks recorded during tACS stimulation. Accuracy is defined as the percentage of correct responses across 10 blocks of the 2-back task and 10 blocks of the 3-back task. The final accuracy measure will be reported as the mean percentage of correct responses separately for the 2-back and 3-back tasks.
Measured: 3.5 years
Accuracy of the verbal 2-back and 3-back tasks after tACS
The outcome measure assesses accuracy in the offline working memory 2-back and 3-back tasks recorded after tACS stimulation. Accuracy is defined as the percentage of correct responses across 6 blocks of the 2-back task and 6 blocks of the 3-back task. The final accuracy measure will be reported as the mean percentage of correct responses separately for the 2-back and 3-back tasks.
Measured: 3.5 years
Reaction times of the visual N-back task in tACS conditions
The Outcome Measure will assess the reaction times during correct responses of the online working memory N-back task (recorded during the stimulations), reported in seconds during 10 blocks of the 2-back task and 10 blocks of the 3-back task.
Measured: 3.5 years
Reaction times of the verbal N-back task after tACS
The Outcome Measure will assess the reaction times during correct responses of the offline working memory N-back task (recorded after the stimulations), reported in seconds during 6 blocks of the 2-back task and 6 blocks of the 3-back task.
Measured: 3.5 years
Secondary outcomes (3)
Cognitive reserve moderator:
Identification of which cognitive reserve proxies or indexes are most effective at moderating tACS-induced changes.
Measured: 3.5 years
tACS-induced functional connectivity changes:
tACS-induced neural changes, including resting-state functional connectivity (rs-FC) within and between large-scale brain networks, dynamic rs-fMRI measures, and task-induced BOLD (Blood-Oxygen-Level Dependent) signal increases assessed at baseline and immediately after each stimulation.
Measured: 3.5 years
Pupillary changes
Measures of pupil dilation during the N-back task performance.
Measured: 3.5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2024
- Study start18 Jun 2022
- Primary completion30 Aug 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AgingStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masaryk University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ilona Eliášová, Ph.D., Principal investigator, Masaryk University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06563453
- Sponsor's protocol ID
- NU21-04-00652
- Status last verified
- Dec 2024
- First submitted
- 19 Aug 2024
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: available upon reasonable request
Publications
Mitterova K, Pupikova M, Gajdos M, Eliasova I, Rektorova I. Optimizing tACS for working memory: differential outcomes in healthy aging and non-amnestic mild cognitive impairment. Alzheimers Res Ther. 2025 Dec 2;18(1):2. doi: 10.1186/s13195-025-01922-4.
PubMed 41331881
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implication of Cognitive Reserve in Non-pharmacological Intervention Outcomes
- ClinicalTrials.gov ID
- NCT06563453
- Acronym / sponsor ID
- NU21-04-00652
- Conditions
- Aging, Mild Cognitive Impairment, Dementia With Lewy Bodies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Masaryk UniversityUniversity, hospital or other
- Study start
- 18 Jun 2022 (actual)
- Primary completion
- 30 Aug 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 20 Aug 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.
Cognitive reserve (CR) is defined as the gradual accumulation of neural resources and their adaptability (i.e., efficiency, capacity, flexibility) due to genetic and/or lifelong environmental factors that mitigate the cognitive effects of age-related processes and brain diseases. Transcranial alternating current stimulation (tACS) can be used to entrain underlying neuronal networks, promoting firing at specific frequencies. Recent studies have demonstrated that fronto-parietal theta oscillatory activity entrainment via tACS leads to working memory enhancement in healthy subjects. However, there remains significant variability in stimulation-induced aftereffects across individuals.
Emerging literature suggests that individual differences, such as CR levels, may be crucial in predicting the benefits of treatment interventions, as they reflect available neural capacity and flexibility. A novel interventional approach is proposed to study CR, utilizing both conventional static proxies, such as premorbid intellect and educational attainment, and dynamic markers, including pupillometry, resting-state, and task-induced functional MRI. By employing cutting-edge noninvasive brain stimulation (NIBS) techniques, the study will acutely modulate network properties to examine the influence of CR on immediate cognitive and brain functional aftereffects induced by the intervention. In addition to focusing on cognitively healthy older adults, this study will, for the first time, include patients with mild cognitive impairment with Lewy bodies (MCI-LB), a prodromal stage of the second most common degenerative dementia after Alzheimer's disease.
Detailed description
A novel interventional approach is proposed for studying cognitive reserve (CR) using dynamic biomarkers, including:
Neuromelanin-sensitive MRI sequences to evaluate signal intensity of the locus coeruleus, Resting-state functional MRI (rs-fMRI) to evaluate network properties such as modularity and local and global efficiency, Baseline dynamic rs-fMRI to evaluate mean dwell time and number of transitions between states, and Baseline task-induced activation to evaluate engagement of "domain-specific" and "domain-general" regions during the 'offline' transfer working memory (WM) task performance, i.e., tasks solved after transcranial alternating current stimulation (tACS).
These dynamic biomarkers are used in addition to established conventional static proxies (education and premorbid intellect).
Specifically, the study aims to:
Assess which CR biomarkers and conventional CR proxies, alone or in combination, best predict the tACS-induced magnitude of cognitive enhancement of the 'online' WM task (solved while stimulated).
Evaluate the influence of CR on the recruitment of compensatory mechanisms (as assessed by task-induced fMRI and rs-fMRI) induced by tACS for solving challenging WM tasks.
Investigate how the CR level moderates the relationship between the magnitude and spatial patterns of brain flexibility changes induced by an acute tACS (as measured by pupil dilation during the online WM task performance and pre-post tACS resting-state functional connectivity changes within and between large-scale brain networks) and cognitive tACS-induced enhancement (as measured by 'online' WM task performance and changes in the 'offline' transfer task performance solved after stimulation).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| sham stimulation | Sham comparator | Device: transcranial alternating current stimulationTwo inactive electrodes (anodes and cathodes) - placed over Medial frontal lobe and Inferior parietal lobe. The flow of current discontinues after 20 seconds, the stimulation continues. |
| frontal stimulation | Experimental | Device: transcranial alternating current stimulationOne active electrode (anode and cathode) - placed over Medial frontal lobe, one inactive electrode (anode and cathode) - placed over Inferior parietal lobe. Current intensity - 2 (milliamperes) mA, frequency: theta 4.51 Hz, stimulation time: 20 minutes |
| frontoparietal stimulation | Experimental | Device: transcranial alternating current stimulationOne active electrode (anode and cathode) - placed over Medial frontal lobe, another active electrode (anode and cathode) - placed over Inferior parietal lobe. Current intensity - 2 mA, frequency: theta 4.51 Hz in-phase, stimulation time: 20 minutes |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Intact cognitive performance as assessed by cognitive evaluation.
- Subjects with possible or probable mild cognitive impairment with Lewy bodies (MCI-LB).
Key exclusion criteria (5 listed)
- Presence of dementia as assessed by a cognitive test battery and evaluation of daily activities.
- Any major psychiatric disorder.
- History of neurological disease affecting the central nervous system (e.g., tumor, epilepsy, stroke, etc.).
- Severe or repeated head injury.
- Non-compensated internal or oncological disease. MRI-incompatible metal in the body (e.g., pacemaker). Left-handedness.
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 |
|---|---|---|
| transcranial alternating current stimulationTranscranial Alternating Current Stimulation (tACS) is a tool that administers a weak alternating current (in the range of 0.1 to 4 mA), most often with a sinusoidal waveform, between electrodes placed over target areas. This can entrain the subjacent neuronal networks favouring the firing at specific frequencies of interest, in certain cases, with effects outlasting the stimulation duration up to 70 min. | Device | frontal stimulation, frontoparietal stimulation, sham stimulation |
Primary outcome
Accuracy of the visual 2-back and 3-back tasks in tACS conditions
Time frame: 3.5 years
The outcome measure assesses accuracy in the online working memory 2-back and 3-back tasks recorded during tACS stimulation. Accuracy is defined as the percentage of correct responses across 10 blocks of the 2-back task and 10 blocks of the 3-back task. The final accuracy measure will be reported as the mean percentage of correct responses separately for the 2-back and 3-back tasks.
Accuracy of the verbal 2-back and 3-back tasks after tACS
Time frame: 3.5 years
The outcome measure assesses accuracy in the offline working memory 2-back and 3-back tasks recorded after tACS stimulation. Accuracy is defined as the percentage of correct responses across 6 blocks of the 2-back task and 6 blocks of the 3-back task. The final accuracy measure will be reported as the mean percentage of correct responses separately for the 2-back and 3-back tasks.
Reaction times of the visual N-back task in tACS conditions
Time frame: 3.5 years
The Outcome Measure will assess the reaction times during correct responses of the online working memory N-back task (recorded during the stimulations), reported in seconds during 10 blocks of the 2-back task and 10 blocks of the 3-back task.
Reaction times of the verbal N-back task after tACS
Time frame: 3.5 years
The Outcome Measure will assess the reaction times during correct responses of the offline working memory N-back task (recorded after the stimulations), reported in seconds during 6 blocks of the 2-back task and 6 blocks of the 3-back task.
3 secondary outcomes
Cognitive reserve moderator:
Time frame: 3.5 years
tACS-induced functional connectivity changes:
Time frame: 3.5 years
Pupillary changes
Time frame: 3.5
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 16 Oct 2026.
- Derived from this study: PubMed 41331881Mitterova K, Pupikova M, Gajdos M, Eliasova I, Rektorova I. Optimizing tACS for working memory: differential outcomes in healthy aging and non-amnestic mild cognitive impairment. Alzheimers Res Ther. 2025 Dec 2;18(1):2. doi: 10.1186/s13195-025-01922-4.
- Individual participant dataSharing planned: No. available upon reasonable request
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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.
Ilona Eliášová, Ph.D. principal investigator
Masaryk University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing transcranial alternating current stimulation in people with Aging and Mild Cognitive Impairment, run by Masaryk University at 1 site in Czechia.
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 2 inclusion and 5 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 16 Oct 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 Czechia. 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?
Accuracy of the visual 2-back and 3-back tasks in tACS conditions (time frame: 3.5 years). The study lists 4 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 NCT06563453, which also lists 1 linked publication.
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 16 Oct 2026.