Prevention of Alzheimer's Disease With CR Plus tDCS in Mild Cognitive Impairment and Depression (PACt-MD)

NCT02386670 | Active Not Recruiting DMC

• 1 other identifier: 041-2014
• Study Type: interventional
• Target: 375
• Locations: 1 country
• Sites: 5

Brief 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 Dementia in older persons with mild cognitive impairment or major depressive disorder with or without mild cognitive impairment.

Conditions

Mild Cognitive Impairment; Major Depressive Disorder, Single Episode, in Full Remission; Major Depressive Disorder, Recurrent, In Remission

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Approximately 4, 12, 24, 36, 48, 60 months after baseline

Study Arms (2)

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).

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).

Other: sham tDCS + sham CR

Interventions

tDCS + CR OTHER

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)

tDCS + CR

sham tDCS + sham CR OTHER

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).

sham tDCS + sham CR

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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
• 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

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• Brain Canada: collaborator
• Applied Health Research Centre: collaborator
• Queen's University: collaborator
• Baycrest Centre for Geriatric Care: collaborator
• Unity Health Toronto: collaborator
• Sunnybrook Health Sciences Centre: collaborator
• University Health Network, Toronto: collaborator

Study Sites (5)

Baycrest Centre for Geriatric Care

Toronto, Ontario, Canada

Location

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, Canada

Location

Sunnybrook Heath Sciences Centre

Toronto, Ontario, Canada

Location

University Health Network

Toronto, Ontario, Canada

Location

Related Publications (5)

• Rajji 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.

  PMID: 39476073 DERIVED

• Marawi 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.

  PMID: 37271418 DERIVED

• Weinstein 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.

  PMID: 34023224 DERIVED

• Chandramouleeshwaran 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.

  PMID: 33846084 DERIVED

• Dham 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.

  PMID: 32323313 DERIVED

Related Links

• 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 Depression
• Brooks et al. 2020. Theta-gamma coupling and ordering information: a stable brain-behavior relationship across cognitive tasks and clinical conditions
• Neufeld et al. 2020. Structural brain networks in remitted psychotic depression
• Goodman et al. 2018. Theta-Gamma Coupling and Working Memory in Alzheimer's Dementia and Mild Cognitive Impairment
• Diniz et al. 2021. Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adults
• 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 Impairment
• Fischer et al. 2019. Examining the Link Between Cardiovascular Risk Factors and Neuropsychiatric Symptoms in Mild Cognitive Impairment and Major Depressive Disorder in Remission
• Yuen et al. 2019. Association between Sleep Disturbances and Medial Temporal Lobe Volume in Older Adults with Mild Cognitive Impairment Free of Lifetime History of Depression
• Brown et al. 2019. Brain Amyloid PET Tracer Delivery is Related to White Matter Integrity in Patients with Mild Cognitive Impairment
• Dham et al. 2020. Functional Competence and Cognition in Individuals With Amnestic Mild Cognitive Impairment
• Rashidi-Ranjbar et al. 2020. Frontal-executive and corticolimbic structural brain circuitry in older people with remitted depression, mild cognitive impairment, Alzheimer's dementia, and normal cognition
• Karameh et al. 2021. Comparing cardiovascular risk factors in older persons with mild cognitive impairment and lifetime history of major depressive disorder
• Chandramouleeshwaran et al. 2021. Relationships between a New Cultured Cell-Based Serum Anticholinergic Activity Assay and Anticholinergic Burden Scales or Cognitive Performance in Older Adults

MeSH Terms

Conditions

Cognitive Dysfunction; Depressive Disorder, Major; Recurrence; Pathologic Complete Response

Interventions

Transcranial Direct Current Stimulation; Cognitive Remediation

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Progression

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Behavior Therapy; Psychotherapy

Study Officials

• Benoit H Mulsant, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Scientist

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 12, 2015
• Study Start: January 1, 2015
• Primary Completion: December 31, 2022
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)