An interventional study of Transcranial Alternating Current Stimulation and Sham tACS in Mild Cognitive Impairment (MCI), sponsored by Centre for Addiction and Mental Health. Recruiting at 1 site in Canada. Open to participants aged 60 Years and older. Per ClinicalTrials.gov, last updated 2026-04-13.
Sponsored by Centre for Addiction and Mental Health · Not applicable, Interventional, and Treatment
This study is looking at a new non-invasive brain stimulation methods called transcranial alternating current stimulation (tACS) to see if it can improve working memory and thinking processes in people with Mild Cognitive Impairment (MCI). tACS is a low-risk, non-painful, low electrical current that circulates through the brain of awake participants and stimulates their brain cells. Participants must be 60 years of age and have a diagnosis of mild cognitive impairment. Participants will undergo treatment sessions that range from 1 to 1.5 hours at CAMH, 5 days a week, over a total of 2 weeks. In addition, participants will complete clinical and cognitive assessments and bloodwork at baseline and again after treatment.
Current treatments for Alzheimer's disease dementia (AD) have limited efficacy probably because by the time AD is manifest it is too late to intervene. Thus, discovering interventions that will prevent AD is highly needed.
Mild Cognitive Impairment (MCI) is a condition that is considered a pre-stage to AD. In MCI, the frontal part of the brain supports the ability to compensate for memory problems which could delay progression to AD. This compensation is supported by "flexible" thinking which includes the ability to hold and manipulate information in mind for brief periods of time (e.g. doing mental math), also called working memory. Working memory has been shown by us and others to depend on the linking of brain waves across multiple brain waves frequencies.
Transcranial Alternating Current Stimulation (tACS) is a non-invasive electrical stimulation, applied to the scalp, that has been shown to improve this linking of brain waves in healthy older individuals. It has also been shown to enhance working memory in older individuals when this linking is enhanced. The effect of tACS on working memory and linking of brain waves in patients with MCI has not been demonstrated yet.
The study investigators propose to study the feasibility and preliminary effects of tACS on TGC and working memory in MCI participants. This proof-of-concept study will test whether tACS engages TGC as a target and, in turn, enhances working memory. Additionally, the investigators will explore the relationship among tACS effects and stress neuroreactivity and neuroimmune/inflammatory response (i.e., the interaction between the nervous system and the immune system), as well as the potential links with working memory.
If successful, our project will serve as a model for a larger trial to confirm the ability of tACS to prevent AD over multiple years of follow-up.
Objective 1: To determine the feasibility of tACS in older individuals with MCI. The investigators will examine recruitment and retention. Hypothesis 1a: At least 30% of screened participants will agree and be eligible to receive the intervention they are assigned to, i.e., tACS. Hypothesis 1b: At least 70% of participants will attend at least 80% of their treatment sessions.
Objective 2: To determine TGC engagement in response to tACS. The investigators will assess whether TGC increases in response to tACS. Hypothesis 2: Participants randomized to tACS will experience higher increase in TGC than those randomized to sham-tACS.
Objective 3: To determine change in working memory in response to tACS, and whether changes in TGC mediate changes in N-back performance with 2-back d' being the primary N-back outcome measure. Hypothesis 3a: Participants randomized to tACS will experience more improvement on N-back from baseline following the intervention than those randomized to sham-tACS. Hypothesis 3b: Across all participants, change in TGC will mediate change in N-back performance.
Exploratory Objective 4: To explore the relationships among tACS effects and stress neuroreactivity and neuroimmune/inflammatory response, as well as the potential links with working memory. Exploratory Hypothesis 4a: Baseline measure of stress neuroreactivity (i.e., salivary α-amylase and cortisol levels) will moderate response to tACS vs. sham-tACS. Exploratory Hypothesis 4b: Baseline measure of neuroimmune/inflammatory response (i.e., s100B, NSE, and MBP / IL-1β, IL-6, CRP, and TNF-α) will moderate response to tACS vs. sham-tACS. Exploratory Hypothesis 4c: Participants randomized to tACS will experience better stress neuroreactivity (i.e., salivary α-amylase and cortisol levels) from baseline following the intervention than those randomized to sham-tACS. Exploratory Hypothesis 4d: Participants randomized to tACS will experience better neuroimmune/inflammatory response (i.e., s100B, NSE, and MBP / IL-1β, IL-6, CRP, and TNF-α) from baseline following the intervention than those randomized to sham-tACS.
Exploratory Mediation Hypothesis: Across all participants, changes in stress neuroreactivity (i.e., salivary α-amylase and cortisol levels) and neuroimmune/inflammatory response (i.e., s100B, NSE, and MBP /I L-1β, IL-6, CRP, and TNF-α) will mediate change in TGC, N-back performance, and working memory.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's planned enrollment of 20 is below the median of 64 across 2,794 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →Centre for Addiction and Mental Health is the lead sponsor of 339 studies on the registry; 51 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Diagnosis of MCI due to AD using the core clinical criteria by the National Institute on Aging and Alzheimer's Association for MCI participants (NIA-AA) and ascertained by a study investigator. The following checklist will be used to ascertain the MCI diagnosis:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
After completing the Baseline testing at Visit 1 and N-back EEG at Visit 2, MCI participants randomized to the active condition will receive a 10-session course of tACS (Visits 4-13), followed by a follow-up assessment, post intervention, at Visit 14.
Device: Transcranial Alternating Current Stimulation
After completing the Baseline testing at Visit 1 and N-back EEG at Visit 2, MCI participants randomized to the sham condition will receive a 10-session course of sham-tACS (Visits 4-13), followed by a follow-up assessment, post intervention, at Visit 14.
Device: Sham tACS
Transcranial Alternating Current Stimulation (tACS) is a non-invasive electrical stimulation that will be used to stimulate the dorsolateral prefrontal cortex (dlPFC) and temporal cortices and in turn enhance Theta-Gamma Coupling (TGC) and working memory in Mild Cognitive Impairment (MCI). Each participant will receive daily stimulation for 10 days. To deliver the tACS, multiple electrodes embedded in a cap placed on the participant's head. Sham-tACS will follow the same procedure.
Also known as: tACS
During sham-tACS, the device will ramp up to the desired intensity over 60 seconds, and then will immediately ramp down, and the stimulation will be shut off, until the end of the session. At the end of the session, the device will again ramp up for 60 seconds and then ramp down. Sham-tACS will also target dlPFC and temporal cortices (similar to active). Each participant will receive daily sham-tACS for 10 days. To deliver the sham-tACS, multiple electrodes will be embedded in a cap placed on the participant's head.
Percentage of All Screened Participants
Recruitment (percentage of all screened participants) will be examined. Hypothesis: At least 30% of screened participants will agree and be eligible to receive the intervention they are assigned to, i.e., tACS.
Time frame: Through treatment completion, at the end of 2-week intervention.
Percentage of All Enrolled Participants
Retention will be examined. Hypothesis: At least 70% of participants will attend at least 80% of their treatment sessions.
Time frame: Through treatment completion, at the end of 2-week intervention.
Theta-gamma Coupling
The modulation index obtained from the EEG recording during N-Back
Time frame: Through treatment completion, at the end of 2-week intervention.
N-Back
Cognitive test via EEG measured by d', a sensitivity index based on the z scores of the hit and false alarm rates using the following formula: d' = z(H)- z(FA) where H is the hit rate and FA is the false alarm rate.
Time frame: Through treatment completion, at the end of 2-week intervention.
Mediation of TGC on changes in N-back performance
The beta value generated by Linear Model examining the association between changes in TGC and changes in N-back performance.
Time frame: Through treatment completion, at the end of 2-week intervention.
PASAT
Modified Paced Auditory Serial Addition Test (PASAT) test total correct responses across both types of trials
Time frame: Through treatment completion, at the end of 2-week intervention.
Neuroimmune response
Measured by concentration of s100B, NSE (pg/mL) in blood sample
Time frame: Through treatment completion, at the end of 2-week intervention.
Neuroimmune response
Measured by concentration of MBP (ng/mL) in blood sample.
Time frame: Through treatment completion, at the end of 2-week intervention.
Inflammatory response
Measured by concentration of IL-1β, IL-6, CRP, and TNF-α (pg/mL) in salivary sample.
Time frame: Through treatment completion, at the end of 2-week intervention.
Stress neuroreactivity
Measured by the dynamics of α-amylase and cortisol levels across baseline phase (before PASAT) and response phase (after PASAT); the intercept, baseline slope, and response slope
Time frame: Through treatment completion, at the end of 2-week intervention.
Plan to share: Yes — IPD used in the results publication can be shared upon a reasonable request.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Analytic code
Time frame: After publishing the results of the study.
Access criteria: New proposals approved by ethics board, data will be shared using Centre for Addiction and Mental Health databank.
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