Electrical Stimulation for Dementia

Overseen By Shelly Rempel-Rossum

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Manitoba

Disqualifiers: Parkinson's, Epilepsy, Bipolar, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks per protocol, 5 days/week

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that participants should not have a change in medication for Alzheimer's disease, dementia, or depression.

What data supports the effectiveness of the treatment Transcranial Direct Current Stimulation (tDCS) for dementia?

Research suggests that tDCS, a noninvasive brain stimulation method, may help slow cognitive decline in Alzheimer's disease, as seen in a case study where a patient's memory improved after 8 months of daily use. Additionally, there is growing evidence that tDCS could play a therapeutic role in delaying cognitive decline in Alzheimer's and mild cognitive impairment. ^{1 2 3 4 5}

Is electrical stimulation for dementia safe for humans?

Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are generally considered safe, with most side effects being mild and temporary. However, there have been rare reports of more serious issues like skin burns and mood changes, and one case of a seizure in a child, though the link to tDCS is unclear. More research is needed, especially for tACS, to fully understand the safety of these treatments. ^{6 7 8 9 10}

How is the treatment of electrical stimulation for dementia different from other treatments?

Electrical stimulation treatments like tDCS and tACS are unique because they are non-invasive methods that use electrical currents to stimulate the brain, potentially improving cognitive function in dementia patients without the need for medication. Unlike traditional drug treatments, these methods focus on directly modulating brain activity to address symptoms. ^{1 2 4 11 12}

What is the purpose of this trial?

Dementia is a prevalent condition with no known cure. It affects not only the person with dementia but also the family. This study will investigate the effects of applying different transcranial electrical stimulation (tES) waveforms to find the optimal stimulation when paired with cognitive exercise on older adults with dementia. It is a placebo-controlled double-blind study with statistical rigor. In addition, the investigators will investigate technological methods to monitor changes due to the intervention. These include functional near infrared spectroscopy (fNIRS), electroencephalography (EEG), electrovestibulography (EVestG), and balance measurements using accelerometers. fNIRS measures oxygenated and deoxygenated blood flow to the brain and it may help to understand neuronal changes due to intervention. EEG measures the electrical activity of the brain via electrodes placed on the scalp to study the brain's response to different electrical stimulations treatments. EVestG is a non-invasive measure of the vestibuloacoustic system in both background (no motion) and in response to passive whole-body tilt stimuli. We hypothesize there is a direct link between vestibular system deficiencies and Alzheimer's. Lastly, the investigators will measure the effects of electrical stimulation on balance by measuring postural sway using two accelerometers. This study investigates the effects of transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) with different protocols for frequencies to determine the most effective treatment to improve cognitive abilities and working memory for people with dementia. The global objective of the proposed study is to investigate the effects of different tES in improving the cognitive status of older adults with dementia, when paired simultaneously with cognitive training. The general objectives include the following: 1. Run a human research randomized and double-blind study to address the global objective of the study with statistical rigor. 2. Investigate the correlation of fNIRS outcomes with those of the primary outcome measures of the study in Objective 1 as well as its predictivity to the treatment at baseline. 3. Investigate the effects of different tES on EEG recordings as well as its predictivity to the treatment at baseline. 4. Investigate the effects of different tES on balance for older adults with cognitive impairment. 5. Investigate the correlation of EVestG outcomes with those of the primary outcome measures of the study in Objective 1 as well as its predictively to the treatment at baseline. 6. Disseminate the project results and design the next follow up project.

Eligibility Criteria

This trial is for older adults aged 50 to 95 with dementia, as indicated by a MoCA score between 5 and 24. It's designed to see if certain brain stimulation techniques can help improve their cognitive abilities.

Inclusion Criteria

My MoCA score is between 5 and 24.

I am between 50 and 95 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different transcranial electrical stimulation (tES) protocols paired with cognitive exercises

4 weeks per protocol, 5 days/week

Daily sessions (in-person or virtual)

Washout

Participants undergo a washout period between different tES treatment protocols

8-20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) within a month after treatment

Open-label extension (optional)

Participants may opt into continuation of the most effective treatment long-term

Long-term

Treatment Details

Interventions

• Transcranial Alternating Current Stimulation (tACS)
• Transcranial Direct Current Stimulation (tDCS)

Trial Overview The study tests different types of transcranial electrical stimulations (tACS and tDCS) combined with cognitive exercises. Participants will be randomly assigned to receive either the actual treatment or a placebo, without knowing which one they are getting.

Participant Groups

Group I: Transcranial Direct Current Stimulation (tDCS) Experimental Treatment 1 Intervention

Participants will receive tDCS simultaneously with cognitive exercises for one month every day excluding weekends.

Group II: Theta Transcranial Alternating Current Stimulation (tACS) Experimental Treatment 1 Intervention

Participants will receive personalized theta tACS simultaneously with cognitive exercises for one month every day excluding weekends.

Group III: Sham Stimulation Experimental Treatment 1 Intervention

Participants will receive sham stimulation simultaneously with cognitive exercises for one month every day excluding weekends.

Group IV: Gamma Transcranial Alternating Current Stimulation (tACS)-Precuneus Experimental Treatment 1 Intervention

Participant will receive tACS at the personalized gamma over the regular placement of electrodes (left dorsolateral prefrontal cortex and the reference electrode on the contralateral supraorbital area) for the first 30-min training session and then over the precuneus (one electrode over Pz on the 10-20 EEG system and the other over the right deltoid muscle) during the second 30-min training session.

Group V: Gamma Transcranial Alternating Current Stimulation (tACS) Experimental Treatment 1 Intervention

Participants will receive personalized gamma tACS simultaneously with cognitive exercises for one month every day excluding weekends.

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Findings from Research

A meta-analysis of 4 studies found that transcranial direct current stimulation (tDCS) alone did not significantly improve the naming ability of patients with dementia.

However, when tDCS was combined with language or cognitive training, it resulted in a large effect size (SMD=0.72), indicating a significant improvement in naming ability for dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Effects of tDCS and Language/Cognitive Intervention on the Naming of Dementia Patients: A Systematic Review and Meta-Analysis. Byeon, H.[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]

A patient with early-onset Alzheimer's disease showed significant improvements in immediate recall (39%) and delayed recall (23%) after daily transcranial direct current stimulation (tDCS) for 8 months, indicating potential cognitive benefits.

The results suggest that tDCS may help stabilize cognitive functions and possibly slow cognitive decline in Alzheimer's disease, warranting further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can 8 months of daily tDCS application slow the cognitive decline in Alzheimer's disease? A case study. Bystad, M., Rasmussen, ID., Grønli, O., et al.[2018]

Transcranial direct current stimulation (tDCS) is gaining recognition as a potential treatment method, especially for individuals who do not respond to or cannot tolerate traditional medications.

The review suggests that large controlled studies should be conducted within the National Health Service (NHS) to further explore the efficacy and practical applications of tDCS in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial stimulation in depression. Allan, C., Kalu, UG., Sexton, CE., et al.[2021]

Transcranial direct current stimulation (tDCS) is a noninvasive technique that can significantly alter brain functions and has been studied in 340 clinical articles for various conditions, including depression, pain syndromes, and neurodegenerative diseases.

The review provides a comprehensive overview of the clinical applications of tDCS, detailing factors such as study design, sample size, and stimulation parameters, which can help guide future research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive database of published tDCS clinical trials (2005-2016). Lefaucheur, JP.[2022]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

Transcranial direct current stimulation (tDCS) is generally considered safe, with most adverse effects being mild and temporary; however, some cases of persistent skin lesions and rare instances of mania or hypomania have been reported, particularly in patients with depression.

Transcranial alternating current stimulation (tACS) has fewer reported adverse events, and no persistent effects have been documented, but more research is needed to fully establish its safety compared to tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of tDCS and tACS: A review. Matsumoto, H., Ugawa, Y.[2020]

High Definition transcranial direct current stimulation (HD-tDCS) is safe and well-tolerated in older adults, with no serious adverse events reported during a study involving 101 participants at stimulation intensities of 2 mA and 3 mA.

The study demonstrated effective blinding, as participants could not accurately distinguish between active and sham stimulation, indicating that HD-tDCS can be reliably used in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. Reckow, J., Rahman-Filipiak, A., Garcia, S., et al.[2020]

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]

Brief bursts of event-related transcranial direct current stimulation (erTDCS) applied to the cerebellum during specific motor actions significantly enhance motor adaptation compared to sham stimulation, as shown in two experiments with improved results from 1-second and 0.5-second stimulation durations.

Standard TDCS applied before or during tasks did not yield the same level of improvement, indicating that timing and duration of stimulation are crucial for efficacy in enhancing motor learning processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short duration event related cerebellar TDCS enhances visuomotor adaptation. Weightman, M., Lalji, N., Lin, CS., et al.[2023]

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]

References

1. Iran pubmed.ncbi.nlm.nih.gov

Combined Effects of tDCS and Language/Cognitive Intervention on the Naming of Dementia Patients: A Systematic Review and Meta-Analysis. [2022]

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

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Can 8 months of daily tDCS application slow the cognitive decline in Alzheimer's disease? A case study. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Transcranial stimulation in depression. [2021]

5. France pubmed.ncbi.nlm.nih.gov

A comprehensive database of published tDCS clinical trials (2005-2016). [2022]

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

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

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

Safety of transcranial direct current stimulation in healthy participants. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events of tDCS and tACS: A review. [2020]

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

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. [2020]

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

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

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

Short duration event related cerebellar TDCS enhances visuomotor adaptation. [2023]

12. Netherlands 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. [2020]