An interventional study of tDCS + CR and sham tDCS + sham CR in Mild Cognitive Impairment, Major Depressive Disorder, Recurrent, In Remission and Major Depressive Disorder, Single Episode, in Full Remission, sponsored by Centre for Addiction and Mental Health. Active, not recruiting at 5 sites in Canada. Open to participants aged 60 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-04-09.
Sponsored by Centre for Addiction and Mental Health · Not applicable, Interventional, and Prevention
This 7-year randomized controlled trial will compare the efficacy of non-invasive brain stimulation (trans-cranial Direct Current Stimulation - tDCS) combined with cognitive remediation (CR) versus sham ("placebo") tDCS combined with sham ("placebo") CR in slowing down cognitive decline and preventing Alzheimer's Dementia in older persons with mild cognitive impairment or major depressive disorder with or without mild cognitive impairment.
By the time Alzheimer's Dementia (AD) and related disorders (ADRD) are diagnosed the brain has sustained substantial insult that limits the efficacy of current treatments. Preventive interventions are urgently needed but prevention studies require large numbers of participants and long follow-up periods unless they can target a high-risk population.
The investigators propose to study the efficacy of a preventive intervention for AD in three high risk groups: (1) older persons with Mild Cognitive Impairment (MCI); (2) older persons with a major depressive disorder (MDD) without MCI; and (3) older persons with MDD and MCI.
MCI is considered a prodromal condition for dementia with a progression rate of about 1% per month. MDD has independently been identified as one of the most promising targets for AD prevention studies since, even after successful treatment of their depressive episode, older persons with remitted MDD develop MCI or dementia at a rate of 1-2% per month.
The investigators proposed intervention is a combination of cognitive remediation (CR) and non-invasive brain stimulation - transcranial Direct Current Stimulation (tDCS). Participants with MCI or MDD (with or without MCI) will be randomized to tDCS + CR or sham ("palcebo") tDCS + sham ("placebo") CR. Both CR and tDCS have been shown to induce neuroplasticity and improve cognition. The investigators hypothesize that their combination will enhance cognitive reserve and protect against cognitive decline and the onset of MCI in those with "normal" cognition or AD in those with MCI.
The investigators design is informed by their experience conducting randomized controlled trials (RCTs) in older participants with dementia, MCI, or MDD over more than two decades. In the investigators recent donepezil prevention trial, combining donepezil with standard antidepressant maintenance prevented cognitive decline and the incidence of dementia in participants who had had both MDD and MCI. Building on this prevention trial, the investigators conceptualize the proposed study as a high-risk, high-gain RCT aimed at enhancing cognitive reserve and preventing cognitive decline and dementia in a high risk population. If the investigators are successful in this high risk population, then tDCS + CR can be tested in, and extended to, the general population (i.e., for universal prevention) or other groups at high risk for AD (i.e., for selective or indicated prevention).
Five Toronto academic sites with a history of successful collaboration will consent up to a total of 500 participants meeting criteria for MCI (age 60 and older) or MDD (age 65 and older) to reach a target of 375 enrolled participants initiating the study intervention. Participants will be randomized to either: i) tDCS + CR or ii) sham tDCS + sham CR. They will first receive tDCS + CR (or sham + sham) 5 days a week for 8 weeks, followed by home-based CR (or sham) and booster sessions of tDCS + CR (or sham + sham) for 5 days every 6 months until they develop dementia (or MCI for those who are deemed cognitively intact at baseline) or complete the study.
During the COVID-19 pandemic, the study has been modified to be administered in a hybrid manner to accommodate both in-person and virtual assessments. Clinical and cognitive assessments (every 12 months) can be done in person or remotely (via telephone or using WebEx/Zoom). Some assessments are modified to accommodate the change in format of administration while maintaining the validity and integrity of the data. The assessments that cannot be done via phone or videoconference will temporarily not be done.
Similarly, the intervention booster group sessions (every 6 months) can also be provided in two formats of in-person or virtual (via WebEx or Zoom) sessions. The tDCS administration cannot be done remotely and hence the virtual booster sessions will only consist of the CR exercises.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's enrollment of 375 is above 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.
Counted across the registry records on this site, refreshed daily.
MCI Group
Inclusion:
Exclusion:
MDD Group
Inclusion:
Meets DSM 5 criteria for one or more MDE(s)with:
Exclusion:
Control group
Inclusion:
Exclusion:
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.
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.
Intervention sessions are administered 5 days/week for 8 weeks (induction phase). Then, for 5 days every 6 months (consolidation phase).Transcranial Direct Current Stimulation (tDCS) session: anode over Fz \& cathode over Iz; direct current: 2 mA (current density=0.57A/m2) for 30 minutes/session at the beginning of each group session. Cognitive Remediation (CR) will also be administered. Sessions last 2 hours each day in a group supervised by trained interventionists. Participants also complete CR exercises online at home. CR consists of computer-based exercises relevant to attention, processing speed, executive function, and verbal and working memory with titrated difficulty levels. Performance feedback will reinforce progress. "Strategic monitoring and bridging discussions" promotes transfer of cognitive gains to everyday tasks. During COVID-19, booster sessions can be provided either in-person or virtually (except for tDCS that cannot be done remotely).
Other: tDCS + CR
First, the intervention sessions will be administered 5 days/week for 8 weeks (induction phase). Then, for 5 days once every 6 months (consolidation phase). tDCS session: anode over Fz \& cathode over Iz; direct current: 2 mA (current density=0.57A/m2) for 1 minute, then the current will be 0 mA for 29 minutes at the beginning of each group session. Cognitive Remediation (CR) will also be administered. Sessions last 2 hours each day in a group supervised by trained interventionists. Participants will also complete CR exercises online at home. CR will consist of computer-based exercises relevant to attention, processing speed, executive function, and verbal and working memory without titrated difficulty levels. During COVID-19, booster sessions can be provided either in-person or virtually (except for sham tDCS that cannot be done remotely).
Other: sham tDCS + sham CR
First, the intervention sessions will be administered 5 days/week for 8 weeks (induction phase). Then, for 5 days once every 6 months (consolidation phase). tDCS session: anode over Fz \& cathode over Iz; direct current: 2 mA (current density=0.57A/m2) for 30 min. at the beginning of each group session. Cognitive Remediation (CR) will also be administered. Sessions last 2 hours each day in a group supervised by trained interventionists. Participants will also complete CR exercises online at home. CR will consist of computer-based exercises relevant to attention, processing speed, executive function, and verbal and working memory with titrated difficulty levels. Performance feedback will reinforce progress. "Strategic monitoring and bridging discussions" will promote transfer of cognitive gains to everyday tasks. During COVID-19, booster sessions can be provided either in-person or virtually (except for tDCS that cannot be done remotely).
Also known as: transcranial Direct Current Stimulation (tDCS), Cognitive Remediation (CR)
First, the intervention sessions will be administered 5 days/week for 8 weeks (induction phase). Then, for 5 days once every 6 months (consolidation phase). tDCS session: anode over Fz \& cathode over Iz; direct current: 2 mA (current density=0.57A/m2) for 1 minute, then the current will be 0 mA for 29 minutes at the beginning of each group session. Cognitive Remediation (CR) will also be administered. Sessions last 2 hours each day in a group supervised by trained interventionists. Participants will also complete CR exercises online at home. CR will consist of computer-based exercises relevant to attention, processing speed, executive function, and verbal and working memory without titrated difficulty levels. During COVID-19, booster sessions can be provided either in-person or virtually (except for sham tDCS that cannot be done remotely).
Change in cognitive scores over time
Z-scores for 18 measures of 12 selected cognitive tests will be calculated based on an healthy comparison group; based on these measures, in turn, z-scores will be averaged into six z-scores for six cognitive domains (executive functioning, language, speed of processing, verbal memory, visual memory, and working memory); finally, the six domain z-scores will be averaged into a composite cognitive score, the change of which is the study primary outcome measure that will be used for H1 and H3.
Time frame: Approximately 4, 12, 24, 36, 48, 60 months after baseline
Percentage of subjects who remain free of MCI or dementia over time
Based on consensus conference diagnosis made according to DSM-5
Time frame: Approximately 4, 12, 24, 36, 48, 60 months after baseline
Plan to share: No
Ran from Jan 2015 to primary completion in Dec 2022, 95 months.
Of 1,442 non-industry interventional studies with no phase under Cognitive Dysfunction, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 51. This study's 95 months is above that.
Counting every sponsor, half of 1,511 studies reached it within 27 months; a quarter within 12 and three quarters within 50.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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