Brain Stimulation + Cognitive Remediation for Preventing Alzheimer's

(PACt-MD Trial)

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antidepressants

Must not be taking: Anticonvulsants, 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: 50

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining brain stimulation (transcranial direct current stimulation, or tDCS) with cognitive exercises (cognitive remediation) can slow memory and thinking problems that might lead to Alzheimer's. It compares real treatments to placebo ones to assess their effectiveness. Individuals with mild memory issues or depression, without severe cognitive problems, might be suitable candidates, especially if they have experienced these conditions for some time. Participants must speak and read English and have a friend or family member to support them during the trial. As an unphased trial, this study offers a chance to contribute to groundbreaking research that could shape future treatments.

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 antidepressants, zopiclone, trazodone, benzodiazepines, gabapentin, and pregabalin 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 brain stimulation and cognitive remediation protocol is safe?

Past studies have found transcranial Direct Current Stimulation (tDCS) to be safe and easy to handle. Some research has reported only mild side effects, such as tingling or itching on the skin where the electrodes are placed. These effects are usually temporary and not serious.

Cognitive Remediation (CR) is a method used to improve thinking and memory skills and is also considered safe. Studies have shown it can enhance memory and other brain functions without causing harm. The exercises, typically done on a computer, are designed to be engaging and low-risk.

Both tDCS and CR have been used in studies with older adults and people with memory issues. They have not been linked to serious safety problems. So far, they seem to be safe options for those looking to slow down memory loss and cognitive decline. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this innovative treatment approach for Alzheimer's because it combines transcranial Direct Current Stimulation (tDCS) with Cognitive Remediation (CR) to enhance cognitive function. Unlike traditional Alzheimer's treatments that often focus on managing symptoms with medication, this method targets brain activity and cognitive skills directly. tDCS uses a mild electrical current to stimulate specific brain regions, potentially improving neural connectivity. Meanwhile, CR offers personalized computer-based exercises to boost cognitive abilities such as memory and attention. This combination offers a proactive approach aimed at slowing cognitive decline, which is a novel direction compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for preventing Alzheimer's?

This trial will compare the effects of combining transcranial Direct Current Stimulation (tDCS) with Cognitive Remediation (CR) against a sham version of both treatments. Research has shown that tDCS can enhance overall thinking skills and attention. Some studies suggest that people with Alzheimer's may benefit more from tDCS than those with mild cognitive impairment (MCI). However, not all studies have shown significant improvements, so results can vary.

CR has shown promise in slowing memory decline over five years for people with MCI. Specifically, participants in those studies demonstrated less decline in daily functioning compared to those who did not receive this training. Overall, combining tDCS and CR might help slow cognitive decline, but individual results can differ. ^{3 4 6 7 8}

Who Is on the Research Team?

Benoit H Mulsant, MD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for older adults over 60 who've had depression or a major depressive episode in the past decade. They must have mild cognitive impairment (MCI) or be stable with no recent substance abuse issues. A study partner is required, and participants need to understand English.

Inclusion Criteria

I have been diagnosed with Mild Cognitive Impairment.

I am over 60 years old.

I am willing to sign the consent form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive tDCS + CR or sham tDCS + sham CR 5 days a week for 8 weeks

8 weeks

40 visits (in-person)

Consolidation Treatment

Participants receive booster sessions of tDCS + CR or sham tDCS + sham CR for 5 days every 6 months

Every 6 months until study completion or development of dementia

10 visits (in-person or virtual) every 6 months

Follow-up

Participants are monitored for cognitive changes and development of dementia

7 years

Annual assessments (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Remediation
• tDCS

Trial Overview The study tests if brain stimulation (tDCS) combined with mental exercises (CR) can slow down memory loss and prevent Alzheimer's compared to placebo treatments, over a period of seven years.

How Is the Trial Designed?

Group I: tDCS + CR Experimental Treatment 1 Intervention

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).

Group II: sham tDCS + sham CR Placebo Group 1 Intervention

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).

Cognitive Remediation is already approved in European Union, United States for the following indications:

Approved in European Union as Cognitive Remediation for:

• Schizophrenia
• Forensic psychiatric rehabilitation

Approved in United States as Cognitive Remediation for:

• Schizophrenia
• Forensic psychiatric rehabilitation

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Queen's University

Collaborator

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Brain Canada

Collaborator

Trials

22

Recruited

6,100+

Applied Health Research Centre

Collaborator

Trials

23

Recruited

70,900+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Baycrest Centre for Geriatric Care

Collaborator

Trials

5

Recruited

540+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10312210/

The Preventing Alzheimer's with Cognitive Training (PACT ... ACTIVE participants randomized to any type of cognitive training further experienced less functional decline across time relative to controls (10).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3979126/

Cognitive training and cognitive rehabilitation for persons with ... Cognitive training and cognitive rehabilitation are specific forms of non-pharmacological intervention to address cognitive and non-cognitive outcomes.

3. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/dad2.12626

Five‐year effects of cognitive training in individuals with mild ... Cognitive training reduced the 5-year memory decline of persons with MCI. Cognitive training also reduced decline on the Montreal Cognitive ...

4. nature.com nature.com/articles/s41746-023-00987-5

Computerized cognitive training for memory functions in ... This meta-analysis evaluated the benefits of computerized cognitive training (CCT) on memory functions in individuals with MCI or dementia.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1279770724002240

Multi-Domain Interventions for Dementia Prevention–A ... Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9344685/

Efficacy of cognitive remediation on activities of daily living in ... Cognitive remediation approaches, including CT, CR, and CS, have been shown to be effective methods in reducing the cognitive decline associated ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10910859/

Digital computerised cognitive training for preventing cognitive ... This study is the first trial to investigate the efficacy of adaptive digital computerised cognitive training in older (≥60 years) patients with ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1041610224027133

Early intervention for cognitive decline CT offers promise as a preventive therapeutic technique in healthy older adults and particularly as a secondary prevention method for “at risk” groups.