Combination of tDCS and Cognitive Rehabilitation for Mild Cognitive Impairment and Late Life Depression

Overseen By Tarek Rajji, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Anticonvulsants, Psychotropics, Cognitive enhancers

Disqualifiers: Schizophrenia, Bipolar, OCD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining brain stimulation (tDCS, a non-invasive treatment) with cognitive exercises can prevent long-term memory and thinking problems in individuals at risk for Alzheimer's disease. The study evaluates the effectiveness of these treatments when performed at home. It involves two groups: one receiving the treatments and another learning to administer them. Suitable participants are those over 60 with mild memory issues or past depression episodes, but not currently experiencing major depression or other significant medical conditions. Participants must be able to read and communicate in English and have a study partner for regular contact. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could shape future Alzheimer's prevention strategies.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially anticonvulsants and some psychotropic drugs, unless they can be safely tapered off. However, some medications like zopiclone, trazodone, benzodiazepines, gabapentin, pregabalin, duloxetine, venlafaxine, or low-dose tricyclic antidepressants are allowed if you've been on a stable dose for at least 4 weeks before joining the study.

What prior data suggests that this combination of tDCS and cognitive rehabilitation is safe?

A previous study tested home-based cognitive exercises combined with a gentle electrical brain stimulation called transcranial direct current stimulation (tDCS) for safety and effectiveness. The research showed that participants generally tolerated this combination well, with no major safety concerns reported.

Another study examined the effects of combining brain training with tDCS and found improvements in attention and memory. This study reported no significant negative effects, suggesting safety for participants.

Additionally, a meta-analysis, which combines results from multiple studies, indicated that using tDCS with cognitive exercises improved thinking skills without major risks. This analysis supports the safety of this treatment approach.

Overall, the evidence suggests that using tDCS with cognitive exercises is a safe option for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using transcranial direct current stimulation (tDCS) combined with cognitive rehabilitation (CR) for mild cognitive impairment and late-life depression because it offers a fresh approach to treatment. Unlike standard treatments that primarily rely on medications or therapy, tDCS + CR aims to directly stimulate brain activity while enhancing cognitive functions through targeted exercises. This dual-action method not only addresses symptoms of depression but also boosts neurocognitive skills like memory and attention. Plus, it's designed to be safe and convenient, allowing patients to receive treatment at home with the help of trained facilitators.

What evidence suggests that this trial's treatments could be effective for mild cognitive impairment and late life depression?

This trial will evaluate the combination of transcranial direct current stimulation (tDCS) and cognitive rehabilitation (CR) for individuals with mild cognitive impairment (MCI) and late-life depression. Research has shown that using tDCS with CR can improve thinking skills. Studies have found that this method can enhance attention, processing speed, and memory in people with MCI and depression. One study discovered that performing tDCS and CR at home was both feasible and safe, leading to better cognitive abilities. A review of multiple studies found significant improvements in thinking skills and daily activities with this combination for those with cognitive difficulties. Overall, these findings suggest that tDCS plus CR could help maintain or improve cognitive abilities. Participants in this trial will either receive tDCS and CR or be trained to facilitate these sessions at home. ^{1 2 3 5 6}

Who Is on the Research Team?

Tarek Rajji, MD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for people over 60 with mild cognitive impairment (MCI) or a history of depression. Participants must meet specific criteria, have had depression in the past decade but currently have low depressive symptoms, and be able to communicate in English. They need a study partner who knows them well. Those with schizophrenia, bipolar disorder, OCD, or recent substance abuse can't join.

Inclusion Criteria

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)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active cognitive remediation and transcranial Direct Current Stimulation (tDCS) at home for 8 weeks

8 weeks

5 sessions per week, at-home

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Facilitate tDCS + CR
• Receive tDCS+CR

Trial Overview

The trial tests an at-home intervention combining transcranial direct current stimulation (tDCS) and cognitive rehabilitation (CR) to see if it can prevent worsening memory and thinking problems in those at risk for Alzheimer's disease.

How Is the Trial Designed?

Group I: Receive tDCS + CR Experimental Treatment 1 Intervention

Receive tDCS+CR: Over the course of 8 weeks, for 5 days a week, participants designated a 'Patient' will receive active tDCS \&CR at-home. tDCS will be administered during the 2 hour CR sessions for 30 min/day. The tDCS montage will be bifrontal91 with 1 large anode placed over Fz and the cathode over Iz. The direct current will be 2 mA (current density = 0.57 A/m2). CR sessions will utilize didactic and computerized drill-based exercises which focus on practice and repetition of neurocognitive ability areas that are affected in depression such as attention, processing speed, executive function, verbal memory, and working memory. Performance feedback is given to reinforce progress and the exercises are designed to be enjoyable to complete, with titrated difficulty levels over time.

Group II: Facilitate tDCS + CR Experimental Treatment 1 Intervention

Over the course of 8 weeks, for 5 days a week, participants designated a 'facilitator' will trained to deliver tDCS \&CR at-home. tDCS will be administered during the 2 hour CR sessions for 30 min/day. The tDCS montage will be bifrontal91 with 1 large anode placed over Fz and the cathode over Iz. The direct current will be 2 mA (current density = 0.57 A/m2). CR sessions will utilize didactic and computerized drill-based exercises which focus on practice and repetition of neurocognitive ability areas that are affected in depression such as attention, processing speed, executive function, verbal memory, and working memory.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

CAMH Foundation

Collaborator

Trials

3

Recruited

910+

Published Research Related to This Trial

In a study involving 11 newly diagnosed stroke patients, the combination of transcranial direct current stimulation (tDCS) and computer-assisted cognitive rehabilitation (CACR) significantly improved cognitive function compared to a control group receiving sham stimulation.

Patients receiving tDCS showed notable enhancements in auditory and visual continuous performance tests, suggesting that targeting the prefrontal cortex with tDCS alongside cognitive training can effectively aid recovery from cognitive dysfunction after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, sham-controlled, pilot study to assess the effects of the concomitant use of transcranial direct current stimulation with the computer assisted cognitive rehabilitation to the prefrontal cortex on cognitive functions in patients with stroke. Park, SH., Koh, EJ., Choi, HY., et al.[2022]

Anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex significantly improved cognitive tasks related to processing speed, selective attention, and planning in five older adults with mild cognitive impairment (MCI).

The study suggests that combining tDCS with cognitive stimulation programs may enhance cognitive performance in individuals with MCI, but further research is needed to explore long-term effects and practical applications in daily life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct Current Stimulation on the Cognitive Functions in Older Adults with Mild Cognitive Impairment: A Pilot Study. Cruz Gonzalez, P., Fong, KNK., Brown, T.[2022]

Transcranial direct current stimulation (tDCS) is a safe and noninvasive method that shows promise in treating cognitive decline associated with Alzheimer's disease and mild cognitive impairment.

The review highlights the need for further large-scale clinical trials to better understand the mechanisms of tDCS and improve its application in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. Pilloni, G., Charvet, LE., Bikson, M., et al.[2022]

Anodal transcranial direct current stimulation (tDCS) significantly improved cognitive performance in healthy elderly individuals by increasing neural activity, as evidenced by enhanced P200 and P300 amplitudes during a working memory task.

Cathodal tDCS also showed potential benefits for Alzheimer's disease patients, increasing P200 amplitude and frontal theta activity, suggesting that tDCS can modulate neural function differently based on the individual's cognitive state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioural and electrophysiological modulations induced by transcranial direct current stimulation in healthy elderly and Alzheimer's disease patients: A pilot study. Cespón, J., Rodella, C., Miniussi, C., et al.[2020]

Transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex improved cognitive function, particularly executive function, in older adults with mild-to-moderate impairments, as evidenced by significant changes in the Montreal Cognitive Assessment scores after ten sessions.

The tDCS intervention also enhanced dual-task standing and walking abilities, with these improvements lasting for at least two weeks, indicating its potential as a safe and effective cognitive-motor intervention for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation May Improve Cognitive-Motor Function in Functionally Limited Older Adults. Manor, B., Zhou, J., Harrison, R., et al.[2019]

This study will evaluate the safety and efficacy of transcranial direct current stimulation (tDCS) combined with cognitive tasks in patients with neurocognitive disorders, using a randomized controlled trial design with 92 participants (46 per group).

The primary outcome will be measured by changes in cognitive function using the Alzheimer Disease Assessment Scale, with additional assessments for depressive symptoms and quality of life, providing a comprehensive evaluation of tDCS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of multisession transcranial direct current stimulation as an augmentation to cognitive tasks in patients with neurocognitive disorders in Japan: a study protocol for a randomised controlled trial. Inagawa, T., Yokoi, Y., Yamada, Y., et al.[2021]

Transcranial direct current stimulation (tDCS) was found to be safe and well-tolerated in a study involving 20 patients with mild or major neurocognitive disorders, with an attrition rate of 0% and no serious adverse events reported.

However, the study did not find any statistically significant improvements in cognitive functioning when comparing the active tDCS group to the sham group, indicating that tDCS may not enhance cognitive performance in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study. Inagawa, T., Yokoi, Y., Narita, Z., et al.[2022]

Citations

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Home-based cognitive remediation and transcranial direct ...

This study demonstrates that home-based CR+tDCS is feasible and safe in patients with MCI or rMDD, and could improve cognition in patients and ...

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pmc.ncbi.nlm.nih.gov/articles/PMC12324912/

Comparison of the Effectiveness of Transcranial Direct Current ...

This study aimed to compare the effectiveness of tDCS and a short-term cognitive rehabilitation protocol on depression and anxiety in patients ...

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frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1523001/full

Effect of transcranial direct current stimulation combined ...

The meta-analysis results indicated that tDCS combined with CR significantly improved cognitive function and ADL among PSCI patients compared ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10823589/

Combined Cognitive Training and Transcranial Direct Current ...

Retained studies included cognitive training combined with active or sham tDCS in a neuropsychiatric population and reported a post-treatment cognitive outcome.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02386670

Study Details | NCT02386670 | Prevention of Alzheimer's ...

This 7-year randomized controlled trial will compare the efficacy of non-invasive brain stimulation (trans-cranial Direct Current Stimulation - tDCS) combined ...

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sciencedirect.com/science/article/pii/S0006322325015379

Impact of tDCS-induced Electric Fields on Slowing ...

The PACt-MD trial (NCT02386670) has shown that combined cognitive remediation (CR) and transcranial direct current stimulation (tDCS) improve ...