Exercise + Brain Stimulation for Vascular Cognitive Impairment

(EXPRESS-V Trial)

Overseen By Kate Survilla

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Benzodiazepines, Psychotropics

Disqualifiers: Stroke, Dementia, Bipolar, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how exercise and brain stimulation can improve memory in individuals with heart-related conditions at risk of cognitive decline. It compares different combinations of exercise and transcranial direct current stimulation (tDCS), a technique believed to boost brain activity. Participants are divided into groups receiving either active tDCS, a sham version, or just exercise guidance. This trial suits those with heart problems, memory struggles, and the ability to exercise at a moderate level. As an unphased trial, it provides a unique opportunity to contribute to understanding new methods for enhancing memory and brain function.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have changed psychotropic medications in the last 4 weeks or are currently using benzodiazepines, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe for people. Studies indicate that tDCS can be used safely for up to 20 days without causing serious side effects. The most common side effects are mild, such as tingling or itching on the skin.

When combining exercise with tDCS, both are safe individually. Exercise improves brain health, and tDCS works well on active brain cells, like those engaged during exercise. This combination is believed to enhance positive effects on brain function.

In summary, both exercise and tDCS have strong safety records, with only mild and temporary side effects. This makes them promising options for people at risk of cognitive decline. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining exercise with brain stimulation techniques like transcranial direct current stimulation (tDCS) for vascular cognitive impairment because this approach targets brain health in a novel way. Unlike traditional treatments that mainly focus on managing risk factors such as blood pressure and cholesterol, these interventions aim to enhance cognitive function directly. Exercise alone is known to improve overall health, but when combined with tDCS, it may boost brain activity by gently stimulating specific brain areas. This synergy has the potential to improve cognitive functions more effectively and quickly than current methods.

What evidence suggests that this trial's treatments could be effective for vascular cognitive impairment?

Research has shown that exercise, one of the treatments in this trial, can greatly improve thinking skills in people with vascular cognitive impairment. Studies have found that aerobic exercise boosts memory and delays the onset of dementia. Exercise also protects the brain from damage caused by small blood vessel disease, which can lead to memory problems.

Transcranial direct current stimulation (tDCS), another treatment option in this trial, has shown mixed results. Some studies suggest tDCS can improve thinking in people with conditions like schizophrenia and depression. However, it has not significantly improved memory in older adults with memory issues. When combined with other treatments, such as cognitive rehabilitation, tDCS might help enhance thinking skills. ^{6 7 8 9 10}

Who Is on the Research Team?

Krista Lanctôt, PhD

Principal Investigator

Sunnybrook Research Institute

Are You a Good Fit for This Trial?

This trial is for English-speaking adults over 50, especially post-menopausal women, with cardiovascular risks or disease and mild memory issues. They must be able to exercise moderately but can't have had a stroke, recent psychotropic medication changes, benzodiazepine use, metal implants affecting brain stimulation safety, or significant neurological/psychiatric conditions.

Inclusion Criteria

I am over 50 and, if female, I am post-menopausal.

Must be able to exercise at a moderate intensity level

Presence of modest deficits (1 standard deviation below population norm) in one of the following domains: executive function, verbal memory, working memory, or visuospatial memory

Exclusion Criteria

Any medical contraindications to exercise

I am currently taking benzodiazepines.

I have had a stroke in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of four interventions: Exercise primer with tDCS, Treatment as usual with tDCS, Exercise primer with sham tDCS, or Treatment as usual with sham tDCS. Interventions include exercise and/or tDCS.

2 weeks

Follow-up

Participants are monitored for cognitive and behavioral changes after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise
• Sham stimulation
• tDCS
• Treatment as usual

Trial Overview The study tests if exercising before brain stimulation (tDCS) improves memory in those at risk of cognitive decline after cardiac rehab. It compares the combination of exercise and tDCS against sham stimulation and usual treatment to see which is more effective.

How Is the Trial Designed?

Group I: Treatment as usual (exercise education) & tDCS Experimental Treatment 2 Interventions

Individuals randomized to this group will receive routine advice about physical activity, and active tDCS.

Group II: Treatment as usual (exercise education) & sham stimulation Experimental Treatment 2 Interventions

Individuals randomized to this group will receive routine advice about physical activity, and sham tDCS.

Group III: Exercise primed tDCS Experimental Treatment 2 Interventions

Individuals randomized to this group will receive exercise at University Health Network-Toronto Rehabilitation Institute followed by active tDCS.

Group IV: Exercise primed Sham stimulation Experimental Treatment 2 Interventions

Individuals randomized to this group will receive exercise at University Health Network-Toronto Rehabilitation Institute followed by sham tDCS.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

Anodal transcranial direct current stimulation (a-tDCS) applied to the primary motor cortex showed a significant improvement in cycling time to exhaustion compared to a sham condition, with an average increase of 93.41 seconds; however, this result was heavily influenced by one study.

Cathodal tDCS (c-tDCS) did not show any significant effects on exercise performance, and a-tDCS did not improve isometric muscle strength, indicating that the benefits of tDCS may be limited to specific types of exercise and require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcranial direct current stimulation on exercise performance: A systematic review and meta-analysis. Machado, DGDS., Unal, G., Andrade, SM., et al.[2019]

In a study involving 12 endurance athletes, neither high-definition tDCS (HD-tDCS) nor conventional tDCS improved exercise performance during time to exhaustion tests, indicating that these stimulation techniques may not enhance athletic performance as hoped.

No serious adverse effects were reported, suggesting that both HD-tDCS and conventional tDCS are safe for use in this context, but the lack of performance improvement may indicate a ceiling effect in exercise capacity among trained athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effect of high-definition and conventional tDCS on exercise performance and psychophysiological responses in endurance athletes: a randomized controlled trial. da Silva Machado, DG., Bikson, M., Datta, A., et al.[2023]

Involuntary exercise induced by functional electrical stimulation (FES) significantly improved recognition memory in rats with vascular dementia, outperforming forced exercise, suggesting its potential as a cognitive rehabilitation tool.

Both voluntary and involuntary exercises enhanced synaptic plasticity in the prefrontal cortex, indicating that FES may strengthen important brain pathways related to memory and learning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise improves recognition memory and synaptic plasticity in the prefrontal cortex for rats modelling vascular dementia. Dong, J., Zhao, J., Lin, Y., et al.[2019]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Transcranial direct current stimulation (tDCS) significantly increased the time to exhaustion (TTE) during submaximal running in trained men, with TTE lasting 21.18 minutes under tDCS compared to 18.44 minutes with sham stimulation.

Despite the improvement in exercise duration, tDCS did not affect the perceived exertion or cardiorespiratory responses (like heart rate and oxygen consumption), suggesting that it enhances endurance without altering physiological stress levels during exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation of motor cortex enhances running performance. Park, SB., Sung, DJ., Kim, B., et al.[2023]

In a study involving 18 chronic stroke patients, bi-hemispheric transcranial direct current stimulation (tDCS) combined with multimodal physical training (MPT) significantly improved motor function and strength compared to sham stimulation, with notable effect sizes in various measures such as Fugl-Meyer scores and peak torque.

The combination of tDCS and MPT led to substantial enhancements in cardiorespiratory capacity and motor performance, indicating that tDCS can effectively optimize rehabilitation outcomes in stroke survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal physical training combined with tDCS improves physical fitness components in people after stroke: a double-blind randomized controlled trial. Massaferri, R., Montenegro, R., de Freitas Fonseca, G., et al.[2023]

Microdermabrasion significantly reduced skin resistance by about 32%, allowing for higher doses of transcranial direct current stimulation (tDCS) without increasing skin sensations or device limitations.

The study found that while microdermabrasion increased perceived sensations slightly when not combined with sonication, overall, it enabled safer and more effective delivery of tDCS by lowering the voltage needed to achieve the same current.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. Chhatbar, PY., Liu, S., Ramakrishnan, V., et al.[2023]

Transcranial direct current stimulation (tDCS) has been found to be safe for use in humans, with no severe complications reported in studies involving both adults and children when applied at intensities of 4 mA or less for up to 60 minutes.

Animal studies indicate that the electrical current used in tDCS is significantly lower than the threshold that could cause permanent changes to brain tissue, suggesting a strong safety profile for this neurorehabilitation method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation in Neurorehabilitation. Ko, MH.[2023]

This study will investigate the combined effects of aerobic exercise and transcranial direct current stimulation (tDCS) on cognitive improvement in patients with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), using a randomized trial design with 10 sessions over 2 weeks.

The primary goal is to assess the efficacy of exercise-primed tDCS on global cognition, while also exploring its impact on specific cognitive domains and neuropsychiatric symptoms, potentially revealing new mechanisms of action for tDCS in enhancing brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise priming with transcranial direct current stimulation: a study protocol for a randomized, parallel-design, sham-controlled trial in mild cognitive impairment and Alzheimer's disease. Liu, CS., Herrmann, N., Song, BX., et al.[2022]

Transcranial direct current stimulation (tDCS) applied to the prefrontal cortex did not affect oxygen uptake (V˙ O2) at rest or during stimulation, indicating it is safe and does not interfere with baseline metabolic functions.

However, when combined with submaximal aerobic exercise, anodal tDCS significantly increased oxygen uptake during the recovery phase, leading to approximately 19% higher energy expenditure compared to a sham condition, suggesting a potential mechanism for enhancing post-exercise recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does prefrontal cortex transcranial direct current stimulation influence the oxygen uptake at rest and post-exercise? Montenegro, R., Okano, AH., Cunha, FA., et al.[2014]

Anodal transcranial direct current stimulation (a-tDCS) did not significantly improve aerobic performance, heart rate, or perceived exertion in a study of 12 highly trained taekwondo athletes, indicating it may not be an effective intervention for enhancing athletic performance.

The study used a randomized, single-blind crossover design, and the results suggest that athletes and coaches should be cautious about using a-tDCS as a performance enhancement tool, as it showed no beneficial effects compared to sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation: No Effect on Aerobic Performance, Heart Rate, or Rating of Perceived Exertion in a Progressive Taekwondo-Specific Test. Mesquita, PHC., Franchini, E., Romano-Silva, MA., et al.[2023]

Transcranial direct current stimulation (tDCS) and aerobic exercise (AE) have shown potential in enhancing neuroplasticity and supporting cognitive and behavioral recovery in psychiatric and neurological conditions, but their individual effects are still limited.

Combining tDCS and AE in a single session may lead to synergistic benefits, particularly in improving executive functions, although more research is needed to understand their interactions and optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Acute Aerobic Exercise and Transcranial Direct Current Stimulation Effects on Cognitive Functions and Their Potential Synergies. Steinberg, F., Pixa, NH., Fregni, F.[2023]

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