Exercise + tDCS for Alzheimer's Disease

(EXACT Trial)

Overseen By Ella Song

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Benzodiazepines

Disqualifiers: Epilepsy, Parkinson's, Schizophrenia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining exercise with brain stimulation can improve memory in individuals with memory problems due to Mild Cognitive Impairment or Alzheimer's disease. The brain stimulation, known as transcranial direct current stimulation (tDCS), uses a small electrical current to target active brain areas. Researchers will divide participants into groups to receive either both exercise and real tDCS, exercise and sham tDCS, or exercise advice and real tDCS. Individuals diagnosed with memory issues related to Alzheimer's who can read and communicate in English may be suitable for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatments for memory improvement.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot join if you've changed cognitive enhancing medications in the last 3 months or anticonvulsants/psychotropic medications in the last month. You also cannot be taking benzodiazepines.

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

Research has shown that both exercise and transcranial direct current stimulation (tDCS) have been studied for their effects on brain health, both separately and together. For individuals with mild cognitive impairment or Alzheimer's disease, researchers have tested tDCS to determine if it can safely improve memory and brain function. A study on tDCS safety found it to be generally well-tolerated, with most participants experiencing only mild side effects like tingling or itching on the scalp where the device is placed.

Exercise is already known to be safe and beneficial for health, especially in older adults, and can help improve memory and slow cognitive decline. When combined with tDCS, it may enhance these positive effects. Overall, previous research considers the treatments in this trial safe. However, anyone interested in participating should consult their doctor about potential side effects and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining exercise with transcranial direct current stimulation (tDCS) for Alzheimer's disease because it offers a novel approach to managing the condition. Traditional treatments often involve medications like donepezil or memantine, which primarily target neurotransmitters. In contrast, tDCS is a non-invasive brain stimulation technique that may enhance cognitive function by modulating neural activity. Additionally, combining tDCS with personalized exercise programs could synergistically improve brain health and cognitive outcomes, offering a more holistic and potentially effective alternative to standard drug therapies.

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

This trial will explore the effects of combining exercise with transcranial direct current stimulation (tDCS) on cognitive function in individuals with Alzheimer's disease. Research has shown that both exercise and tDCS can improve thinking and memory in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Exercise alone boosts overall brain health and specific thinking skills in older adults with MCI. Studies indicate that tDCS can significantly enhance general thinking abilities and focus. In this trial, some participants will receive both exercise and active tDCS, while others will receive exercise with sham tDCS or exercise education with active tDCS. Combining exercise and tDCS might be even more effective, particularly in improving thinking skills in those with dementia. Overall, this combination appears promising for helping people with MCI and AD improve their memory and thinking abilities. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals over 50 with mild Alzheimer's or cognitive impairment who can communicate in English and have an MMSE score of at least 19. It's not suitable for those recently changing medication, using benzodiazepines, having metal implants like pacemakers, other significant neurological conditions, psychiatric disorders, substance use disorder, or medical reasons preventing exercise.

Inclusion Criteria

Mild severity of impairment (standardized Mini-Mental State Examination (MMSE) score ≥19)

I have been diagnosed with Alzheimer's or a mix of Alzheimer's and vascular cognitive impairment.

Ability to read and communicate in English

Exclusion Criteria

I haven't changed my seizure or mood medications in the last month.

I haven't changed my dementia medication in the last 3 months.

I am currently taking benzodiazepines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combined exercise and tDCS intervention or control interventions over a 2-week period

2 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for changes in cognitive function and neuropsychiatric symptoms

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise
• tDCS

Trial Overview

The study tests if brain stimulation (tDCS) combined with exercise improves memory in people with Mild Cognitive Impairment or Alzheimer's. Participants will receive either real tDCS while exercising or a sham treatment without active stimulation alongside exercise education.

How Is the Trial Designed?

Group I: Exercise and tDCS Experimental Treatment 2 Interventions

Patients randomized to this group will attend Toronto Rehabilitation Institute - University Health Network (TRI-UHN) for an individualized exercise program and active tDCS intervention.

Group II: Exercise and Sham tDCS Experimental Treatment 2 Interventions

Patients randomized to this group will attend TRI-UHN for an individualized exercise program and sham tDCS intervention.

Group III: Exercise Education and tDCS Experimental Treatment 2 Interventions

Patients randomized to this group will undergo treatment as usual, receiving routine advice about physical activity and active tDCS intervention.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

In a study involving 10 patients with Alzheimer's disease, anodal transcranial direct current stimulation (AtDCS) significantly improved recognition memory performance, while cathodal tDCS (CtDCS) led to a decline in performance.

tDCS is shown to be a safe and inexpensive method that could enhance cognitive function in Alzheimer's patients, suggesting potential for further research on its use alongside other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Ferrucci, R., Mameli, F., Guidi, I., et al.[2022]

A 16-week supervised aerobic exercise program for 200 patients with mild Alzheimer's disease did not show significant improvements in overall cognitive performance or quality of life compared to a control group.

However, the exercise program significantly reduced neuropsychiatric symptoms and showed potential cognitive benefits in patients who adhered closely to the exercise regimen, indicating that regular, intense exercise may help improve certain aspects of cognitive function in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial. Hoffmann, K., Sobol, NA., Frederiksen, KS., et al.[2022]

Exercise can be an effective treatment for Alzheimer's disease (AD), showing improvements in cognitive function, reduced neuropsychiatric symptoms, and slower decline in daily activities, making it a valuable intervention alongside traditional medications.

Physical inactivity is a major preventable risk factor for developing AD, and higher levels of physical activity are linked to a lower risk of disease, highlighting the importance of exercise in both prevention and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzheimer's Disease and Exercise: A Literature Review. Cass, SP.[2017]

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]

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]

Two patients with amnestic mild cognitive impairment (MCI) who engaged in regular vigorous exercise showed minimal progression to Alzheimer's disease (AD) over 8 to 16 years, suggesting that such exercise may help slow disease progression.

Both patients maintained stable cognitive function, as indicated by their Montreal Cognitive Assessment scores, despite having positive AD biomarkers, highlighting the potential protective effects of vigorous exercise against cognitive decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vigorous, regular physical exercise may slow disease progression in Alzheimer's disease. Devanand, DP., Masurkar, AV., Wisniewski, T.[2023]

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]

A systematic review of six studies involving community-dwelling older adults with Alzheimer's-type dementia found trends toward improvement in executive function scores due to physical exercise, with significant improvements noted in four of the studies.

The findings suggest that physical exercise may have a beneficial effect on cognitive functions like attention and memory in individuals with Alzheimer's-type dementia, highlighting the need for further research on the recommended 150 minutes of exercise per week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of physical exercise on executive function in community-dwelling older adults living with Alzheimer's-type dementia: A systematic review. Guitar, NA., Connelly, DM., Nagamatsu, LS., et al.[2022]

In a study of 91,298 older adults, vigorous physical activity (VPA) was found to significantly reduce Alzheimer's disease-related mortality, with optimal benefits observed at 140 minutes per week, potentially preventing up to 37,710 deaths annually in the U.S.

Moderate physical activity (MPA) did not show a significant association with Alzheimer's disease-related mortality, highlighting the greater importance of VPA for health outcomes in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate and vigorous leisure time physical activity in older adults and Alzheimer's disease-related mortality in the USA: a dose-response, population-based study. López-Bueno, R., Yang, L., Stamatakis, E., et al.[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]

Transcranial direct current stimulation (tDCS) significantly improved cognitive function in patients with mild to moderate Alzheimer's disease, based on a meta-analysis of seven studies involving 146 patients, with a standardized mean difference of 0.37.

Single sessions of tDCS were effective, particularly when stimulating the temporal cortex, while repeated sessions and lower current densities did not show significant benefits, highlighting the need for careful consideration of treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis. Cai, M., Guo, Z., Xing, G., et al.[2020]

In a study involving 34 Alzheimer's disease patients, both anodal and cathodal transcranial direct current stimulation (tDCS) significantly improved cognitive function as measured by the mini-mental state examination (MMSE) compared to sham stimulation.

tDCS also reduced the P300 latency, a measure associated with cognitive processing, indicating potential benefits in neurorehabilitation for Alzheimer's patients, although it did not affect motor cortex excitability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer's disease. Khedr, EM., Gamal, NF., El-Fetoh, NA., et al.[2022]

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frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1454755/full

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This study aims to determine the feasibility and safety of applying tDCS treatment using optimized and personalized tDCS electrode positions in patients with ...