Mild Cognitive ImpairmentPACt-MDNCT02386670
Prevention of Alzheimer's Disease With CR Plus tDCS in Mild Cognitive Impairment and Depression (PACt-MD)
A study testing tDCS + CR in people with Mild Cognitive Impairment and Major Depressive Disorder, Recurrent, In Remission, run by Centre for Addiction and Mental Health at 5 sites in Canada.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment, Major Depressive Disorder, Recurrent, In Remission, Major Depressive Disorder, Single Episode, in Full Remission
- What is being tested?
- tDCS + CR
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 375 participants
- Where
- 5 sitesCanada
- Study dates
- Jan 2015to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age > 60 (on day of randomization)
- DSM 5 criteria for Mild Neurocognitive Disorder ("MCI")
- Willingness to provide informed consent
- MADRS score of 10 or below
- Availability of a study partner who has regular contact with the participant
- Ability to read and communicate in English (with corrected vision and hearing, if needed)
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- Age ≥ 65 (on day of randomization)
- Meets DSM 5 criteria for one or more MDE(s)with:
- an offset of 2 months to 5 years from the screening visit date. It is not necessary for this (these) episode(s) to have received medical attention OR
- an offset of 5 years or more from the screening visit date. It is necessary that at least one MDE received medical attention (e.g., previously been on one or more antidepressant(s), saw a psychiatrist, primary care physician, or had a previous hospitalization). Also, the MDE must have occurred during the participant's adult life (i.e., at 18 years of age or older).
- MADRS score of 10 or below
- Willingness to provide informed consent
- Availability of a study partner who has regular contact with the participant
- Ability to read and communicate in English (with corrected vision and hearing, if needed)
- Age > 60
- MADRS score of 10 or below
- Willingness to provide informed consent
- Ability to read and communicate in English (with corrected vision and hearing, if needed)
Who cannot join
- Met DSM 5 criteria for Major Depressive Episode in past 10 years
- Lifetime DSM 5 diagnosis of schizophrenia, bipolar disorder, or OCD
- DSM 5 diagnosis of alcohol or other substances use disorder within the past 12 months
- High risk for suicide
- Significant neurological condition (e.g., stroke, seizure disorder, MS)
- Unstable medical illness, (e.g., uncontrolled diabetes mellitus or hypertension)
Show all 28Show fewer
- Having taken a cognitive enhancer (acetylcholinesterase inhibitor or memantine) within the past 6 weeks.
- Participants taking anticonvulsants, and other psychotropic medication (see exceptions below) that cannot be safely tapered and discontinued. The following psychotropic medications are allowed: i) any antidepressant; ii) zopiclone, trazadone, or a benzodiazepine if they have been taken at a stable dose for at least 4 weeks prior to study entry and; iii) gabapentin and pregabalin if they have been taken at a stable dose for at least 4 weeks prior to study entry AND if prescribed for chronic pain.
- A pace-maker or other metal implants that would preclude safe use of tDCS.
- MDD Group
- Meets DSM 5 criteria for Major Neurocognitive Disorder ("dementia")
- Lifetime DSM 5 diagnosis of schizophrenia, bipolar disorder, or OCD
- DSM 5 diagnosis of alcohol or other substances use disorder within the past 12 months.
- High risk for suicide.
- Significant neurological condition (e.g., stroke, seizure disorder, MS)
- Unstable medical illness (e.g., uncontrolled diabetes mellitus or hypertension)
- Participants taking anticonvulsants, and other psychotropic medication (see exception below) that cannot be safely tapered and discontinued. In addition to any antidepressant, the following psychotropic medications are allowed if they have been taken at a stable dose for at least 4 weeks prior to study entry: zopiclone, trazodone, or a benzodiazepine; and gabapentin or pregabalin if prescribed for chronic pain.
- Having taken a cognitive enhancer (acetylcholinesterase inhibitor or memantine) within the past 6 weeks.
- A pace-maker or other metal implants that would preclude safe use of tDCS.
- Received electroconvulsive therapy (ECT) within 6 months of baseline neruopsychological testing.
- Control group
- Meets DSM 5 criteria for Minor or Major Neurocognitive Disorder
- Any other lifetime DSM 5 diagnosis except for simple/specific phobias
- Significant neurological condition (e.g., stroke, seizure disorder, MS)
- Unstable medical illness, (e.g., uncontrolled diabetes mellitus or hypertension)
- Participants taking anticonvulsants, and other psychotropic medication (see exception below) that cannot be safely tapered and discontinued. The following psychotropic medications are allowed if they have been taken at a stable dose for at least 4 weeks: zopiclone up to 15 mg/day; trazadone up to 150 mg/day; benzodiazepine at a dose of up to 3 mg/day lorazepam-equivalents; gabapentin and pregabalin (if prescribed for pain).
- A pace-maker or other metal implants
- Neuropsychological testing within the past 12 months
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
Baycrest Centre for Geriatric Care
Toronto, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario
St. Michael's Hospital
Toronto, Ontario
Sunnybrook Heath Sciences Centre
Toronto, Ontario
University Health Network
Toronto, Ontario
About this study
Official title: Prevention of Alzheimer's Dimentia With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression
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.
Read the detailed description
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.
- Conditions
- Mild Cognitive Impairment, Major Depressive Disorder, Recurrent, In Remission, Major Depressive Disorder, Single Episode, in Full Remission
- Being tested
- tDCS + CR, sham tDCS + sham CR
- Medical subject headings
- Cognitive Dysfunction, Depressive Disorder, Major, Recurrence, Pathologic Complete Response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tDCS + CROther
Also called 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 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).
sham tDCS + sham CROther
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).
| Study group | Role | What they receive |
|---|---|---|
| tDCS + CR | Experimental | 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). Receives: Other: tDCS + CR |
| sham tDCS + sham CR | Sham comparator | 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). Receives: Other: sham tDCS + sham CR |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 4, 12, 24, 36, 48, 60 months after baseline
Secondary outcomes (1)
Percentage of subjects who remain free of MCI or dementia over time
Based on consensus conference diagnosis made according to DSM-5
Measured: Approximately 4, 12, 24, 36, 48, 60 months after baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2015 (estimated)
- Study startJan 2015
- Primary completion31 Dec 2022
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 375 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Brain Canada, Applied Health Research Centre, Queen's University, Baycrest Centre for Geriatric Care, Unity Health Toronto, Sunnybrook Health Sciences Centre, University Health Network, Toronto
- Responsible party
- Principal investigator, Benoit Mulsant, Centre for Addiction and Mental Health
- Investigators
- Benoit H Mulsant, MD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02386670
- Sponsor's protocol ID
- 041-2014
- Acronym
- PACt-MD
- Status last verified
- Apr 2026
- First submitted
- 27 Feb 2015
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Brooks H, Mirjalili M, Ma C, Blumberger DM, Bowie CR, Fischer CE, Flint AJ, Herrmann N, Kumar S, Lanctot K, Mah L, Mulsant B, Pollock BG, Schoer N, Zomorrodi R, Rajji TK. The effect of theta-gamma coupling on response to cognitive remediation combined with transcranial direct current stimulation in older adults at high risk for dementia: a PACt-MD secondary analysis. Neuropsychopharmacology. 2026 Aug 13. doi: 10.1038/s41386-026-02524-w. Online ahead of print.
PubMed 42595848Song BX, Schecter J, Vieira E, Gallagher D, Diniz BS, Fischer CE, Flint AJ, Herrmann N, Kennedy JL, Mah L, Mulsant B, Pollock BG, Rajji TK, Ma C, Lanctot KL; PACt-MD Study Group. Angiogenesis markers and cognitive response in a randomized trial of cognitive remediation plus transcranial direct current stimulation in older adults at risk of dementia. J Alzheimers Dis. 2026 Aug;112(3):1314-1323. doi: 10.1177/13872877261457934. Epub 2026 Jun 16.
PubMed 42300721Ho NCW, Zhukovsky P, Rajji TK, Bowie CR, Brooks H, Butters MA, Chen Y, Fischer CE, Flint AJ, Herrmann N, Lanctot KL, Lee A, Mah L, Marawi T, Pollock BG, Ryan JD, Schoer N, Ma C, Voineskos AN, Mulsant BH; PACt-MD Study Group. Brain Structures and Cognitive Decline: Moderation Analysis of the PACt-MD Randomized Clinical Trial of Brain Stimulation Plus Cognitive Remediation in Older Adults With Remitted Depression or Mild Cognitive Impairment. Am J Geriatr Psychiatry. 2026 Aug;34(8):1005-1015. doi: 10.1016/j.jagp.2026.04.008. Epub 2026 Apr 30.
PubMed 42203570Rajji TK, Bowie CR, Herrmann N, Pollock BG, Lanctot KL, Kumar S, Flint AJ, Mah L, Fischer CE, Butters MA, Bikson M, Kennedy JL, Blumberger DM, Daskalakis ZJ, Gallagher D, Rapoport MJ, Verhoeff NPLGP, Golas AC, Graff-Guerrero A, Vieira E, Voineskos AN, Brooks H, Melichercik A, Thorpe KE, Mulsant BH; PACt-MD Study Group. Slowing Cognitive Decline in Major Depressive Disorder and Mild Cognitive Impairment: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Jan 1;82(1):12-21. doi: 10.1001/jamapsychiatry.2024.3241.
PubMed 39476073Marawi T, Zhukovsky P, Rashidi-Ranjbar N, Bowie CR, Brooks H, Fischer CE, Flint AJ, Herrmann N, Mah L, Pollock BG, Rajji TK, Tartaglia MC, Voineskos AN, Mulsant BH; PACt-MD Study Group. Brain-Cognition Associations in Older Patients With Remitted Major Depressive Disorder or Mild Cognitive Impairment: A Multivariate Analysis of Gray and White Matter Integrity. Biol Psychiatry. 2023 Dec 15;94(12):913-923. doi: 10.1016/j.biopsych.2023.05.018. Epub 2023 Jun 2.
PubMed 37271418Weinstein AM, Gujral S, Butters MA, Bowie CR, Fischer CE, Flint AJ, Herrmann N, Kennedy JL, Mah L, Ovaysikia S, Pollock BG, Rajji TK, Mulsant BH; PACt-MD Study Group.. Diagnostic Precision in the Detection of Mild Cognitive Impairment: A Comparison of Two Approaches. Am J Geriatr Psychiatry. 2022 Jan;30(1):54-64. doi: 10.1016/j.jagp.2021.04.004. Epub 2021 Apr 14.
PubMed 34023224Chandramouleeshwaran S, Ahsan N, Raymond R, Nobrega JN, Wang W, Fischer CE, Flint AJ, Herrmann N, Kumar S, Lanctot K, Mah L, Mulsant BH, Pollock BG, Rajji TK. Relationships Between a New Cultured Cell-Based Serum Anticholinergic Activity Assay and Anticholinergic Burden Scales or Cognitive Performance in Older Adults. Am J Geriatr Psychiatry. 2021 Dec;29(12):1239-1252. doi: 10.1016/j.jagp.2021.03.002. Epub 2021 Mar 18.
PubMed 33846084Dham P, Bingham KS, Bowie CR, Butters MA, Fischer CE, Flint A, Herrmann N, Kumar S, Mah L, Mulsant BH, Pollock BG, Rajji TK; for PACt-MD Study Group. Functional Competence and Cognition in Individuals With Amnestic Mild Cognitive Impairment. J Am Geriatr Soc. 2020 Aug;68(8):1787-1795. doi: 10.1111/jgs.16454. Epub 2020 Apr 22.
PubMed 32323313
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Alzheimer's Dimentia With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression
- ClinicalTrials.gov ID
- NCT02386670
- Acronym / sponsor ID
- PACt-MD / 041-2014
- Conditions
- Mild Cognitive Impairment, Major Depressive Disorder, Recurrent, In Remission, Major Depressive Disorder, Single Episode, in Full Remission
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 375 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Brain Canada, Applied Health Research Centre, Queen's University, Baycrest Centre for Geriatric Care, Unity Health Toronto, Sunnybrook Health Sciences Centre, University Health Network, Toronto
- Study start
- Jan 2015 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 12 Mar 2015 (estimated)
- 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.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tDCS + CR | Experimental | Other: tDCS + CRIntervention 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). |
| sham tDCS + sham CR | Sham comparator | Other: sham tDCS + sham CRFirst, 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). |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age > 60 (on day of randomization)
- DSM 5 criteria for Mild Neurocognitive Disorder ("MCI")
- Willingness to provide informed consent
- MADRS score of 10 or below
- Availability of a study partner who has regular contact with the participant
Key exclusion criteria (28 listed)
- Met DSM 5 criteria for Major Depressive Episode in past 10 years
- Lifetime DSM 5 diagnosis of schizophrenia, bipolar disorder, or OCD
- DSM 5 diagnosis of alcohol or other substances use disorder within the past 12 months
- High risk for suicide
- Significant neurological condition (e.g., stroke, seizure disorder, MS)
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 |
|---|---|---|
| tDCS + CRAlso: 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 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). | Other | tDCS + CR |
| sham tDCS + sham CRFirst, 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 |
Primary outcome
Change in cognitive scores over time
Time frame: Approximately 4, 12, 24, 36, 48, 60 months after baseline
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.
1 secondary outcome
Percentage of subjects who remain free of MCI or dementia over time
Time frame: Approximately 4, 12, 24, 36, 48, 60 months after baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Derived from this study: PubMed 42595848Brooks H, Mirjalili M, Ma C, Blumberger DM, Bowie CR, Fischer CE, Flint AJ, Herrmann N, Kumar S, Lanctot K, Mah L, Mulsant B, Pollock BG, Schoer N, Zomorrodi R, Rajji TK. The effect of theta-gamma coupling on response to cognitive remediation combined with transcranial direct current stimulation in older adults at high risk for dementia: a PACt-MD secondary analysis. Neuropsychopharmacology. 2026 Aug 13. doi: 10.1038/s41386-026-02524-w. Online ahead of print.
- Derived from this study: PubMed 42300721Song BX, Schecter J, Vieira E, Gallagher D, Diniz BS, Fischer CE, Flint AJ, Herrmann N, Kennedy JL, Mah L, Mulsant B, Pollock BG, Rajji TK, Ma C, Lanctot KL; PACt-MD Study Group. Angiogenesis markers and cognitive response in a randomized trial of cognitive remediation plus transcranial direct current stimulation in older adults at risk of dementia. J Alzheimers Dis. 2026 Aug;112(3):1314-1323. doi: 10.1177/13872877261457934. Epub 2026 Jun 16.
- Derived from this study: PubMed 42203570Ho NCW, Zhukovsky P, Rajji TK, Bowie CR, Brooks H, Butters MA, Chen Y, Fischer CE, Flint AJ, Herrmann N, Lanctot KL, Lee A, Mah L, Marawi T, Pollock BG, Ryan JD, Schoer N, Ma C, Voineskos AN, Mulsant BH; PACt-MD Study Group. Brain Structures and Cognitive Decline: Moderation Analysis of the PACt-MD Randomized Clinical Trial of Brain Stimulation Plus Cognitive Remediation in Older Adults With Remitted Depression or Mild Cognitive Impairment. Am J Geriatr Psychiatry. 2026 Aug;34(8):1005-1015. doi: 10.1016/j.jagp.2026.04.008. Epub 2026 Apr 30.
- Derived from this study: PubMed 39476073Rajji TK, Bowie CR, Herrmann N, Pollock BG, Lanctot KL, Kumar S, Flint AJ, Mah L, Fischer CE, Butters MA, Bikson M, Kennedy JL, Blumberger DM, Daskalakis ZJ, Gallagher D, Rapoport MJ, Verhoeff NPLGP, Golas AC, Graff-Guerrero A, Vieira E, Voineskos AN, Brooks H, Melichercik A, Thorpe KE, Mulsant BH; PACt-MD Study Group. Slowing Cognitive Decline in Major Depressive Disorder and Mild Cognitive Impairment: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Jan 1;82(1):12-21. doi: 10.1001/jamapsychiatry.2024.3241.
- Derived from this study: PubMed 37271418Marawi T, Zhukovsky P, Rashidi-Ranjbar N, Bowie CR, Brooks H, Fischer CE, Flint AJ, Herrmann N, Mah L, Pollock BG, Rajji TK, Tartaglia MC, Voineskos AN, Mulsant BH; PACt-MD Study Group. Brain-Cognition Associations in Older Patients With Remitted Major Depressive Disorder or Mild Cognitive Impairment: A Multivariate Analysis of Gray and White Matter Integrity. Biol Psychiatry. 2023 Dec 15;94(12):913-923. doi: 10.1016/j.biopsych.2023.05.018. Epub 2023 Jun 2.
- Derived from this study: PubMed 34023224Weinstein AM, Gujral S, Butters MA, Bowie CR, Fischer CE, Flint AJ, Herrmann N, Kennedy JL, Mah L, Ovaysikia S, Pollock BG, Rajji TK, Mulsant BH; PACt-MD Study Group.. Diagnostic Precision in the Detection of Mild Cognitive Impairment: A Comparison of Two Approaches. Am J Geriatr Psychiatry. 2022 Jan;30(1):54-64. doi: 10.1016/j.jagp.2021.04.004. Epub 2021 Apr 14.
- Derived from this study: PubMed 33846084Chandramouleeshwaran S, Ahsan N, Raymond R, Nobrega JN, Wang W, Fischer CE, Flint AJ, Herrmann N, Kumar S, Lanctot K, Mah L, Mulsant BH, Pollock BG, Rajji TK. Relationships Between a New Cultured Cell-Based Serum Anticholinergic Activity Assay and Anticholinergic Burden Scales or Cognitive Performance in Older Adults. Am J Geriatr Psychiatry. 2021 Dec;29(12):1239-1252. doi: 10.1016/j.jagp.2021.03.002. Epub 2021 Mar 18.
- Derived from this study: PubMed 32323313Dham P, Bingham KS, Bowie CR, Butters MA, Fischer CE, Flint A, Herrmann N, Kumar S, Mah L, Mulsant BH, Pollock BG, Rajji TK; for PACt-MD Study Group. Functional Competence and Cognition in Individuals With Amnestic Mild Cognitive Impairment. J Am Geriatr Soc. 2020 Aug;68(8):1787-1795. doi: 10.1111/jgs.16454. Epub 2020 Apr 22.
- Rajji et al. 2020. Design and Rationale of the PACt-MD Randomized Clinical Trial: Prevention of Alzheimer's dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and DepressionLink provided by the sponsor.
- Brooks et al. 2020. Theta-gamma coupling and ordering information: a stable brain-behavior relationship across cognitive tasks and clinical conditionsLink provided by the sponsor.
- Neufeld et al. 2020. Structural brain networks in remitted psychotic depressionLink provided by the sponsor.
- Goodman et al. 2018. Theta-Gamma Coupling and Working Memory in Alzheimer's Dementia and Mild Cognitive ImpairmentLink provided by the sponsor.
- Diniz et al. 2021. Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adultsLink provided by the sponsor.
- Goodman et al. 2019. Changes in Theta but not Alpha Modulation Are Associated with Impairment in Working Memory in Alzheimer's Disease and Mild Cognitive ImpairmentLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Benoit H Mulsant, MD principal investigator
Centre for Addiction and Mental Health
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing tDCS + CR in people with Mild Cognitive Impairment and Major Depressive Disorder, Recurrent, In Remission, run by Centre for Addiction and Mental Health at 5 sites in Canada.
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 18 inclusion and 28 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: under way, not looking for participants, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. 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?
This study is still under way. Results are not available in the source record yet.
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 cognitive scores over time (time frame: Approximately 4, 12, 24, 36, 48, 60 months after baseline). 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 NCT02386670, which also lists 8 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 9 Apr 2026.