Exercise + Brain Stimulation for Vascular Cognitive Impairment

(EXPRESS-V Trial)

Overseen By Vivian Feng

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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

People with vascular conditions are at risk of having memory problems, and these memory problems increase the risk for further cognitive decline. Brain stimulation has been used to improve mood and memory. Transcranial direct current stimulation (tDCS) is believed to work best on brain cells that are active or "primed" before stimulation. The purpose of this study is to compare the effects of exercise and tDCS on memory performance in patients who have completed cardiac rehabilitation and are at risk of cognitive decline.

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.

What data supports the effectiveness of the treatment Exercise + Brain Stimulation for Vascular Cognitive Impairment?

Research suggests that combining exercise with transcranial direct current stimulation (tDCS) may enhance brain function, as exercise increases brain activity, potentially making tDCS more effective. Studies have shown that tDCS can improve cognitive function in conditions like mild cognitive impairment and Alzheimer's disease, and enhance physical performance, indicating potential benefits for vascular cognitive impairment. ^{1 2 3 4 5}

Is the combination of exercise and transcranial direct current stimulation (tDCS) safe for humans?

Research shows that transcranial direct current stimulation (tDCS) is generally safe for humans when used at conventional levels (up to 4 milliamperes for 40 minutes) and has not resulted in serious adverse effects across thousands of sessions. Exercise is also widely recognized as safe for most people. Combining these two methods has not shown any severe side effects, but more research is needed to fully understand their interactions. ^{3 6 7 8 9}

How does the treatment of exercise combined with tDCS differ from other treatments for vascular cognitive impairment?

This treatment is unique because it combines physical exercise with transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that can enhance exercise performance and potentially improve cognitive function by modulating brain activity. Unlike traditional treatments, this approach targets both physical and cognitive aspects, potentially offering a more comprehensive benefit for vascular cognitive impairment. ^{2 3 10 11 12}

Research Team

Krista Lanctôt, PhD

Principal Investigator

Sunnybrook Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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) 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) 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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. England 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation of motor cortex enhances running performance. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Does prefrontal cortex transcranial direct current stimulation influence the oxygen uptake at rest and post-exercise? [2014]

5. United States 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Review of Acute Aerobic Exercise and Transcranial Direct Current Stimulation Effects on Cognitive Functions and Their Potential Synergies. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. [2023]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

Effect of transcranial direct current stimulation on exercise performance: A systematic review and meta-analysis. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Exercise improves recognition memory and synaptic plasticity in the prefrontal cortex for rats modelling vascular dementia. [2019]

12. England 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. [2023]