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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how different types of electrical stimulation on the brain, combined with cognitive exercises, can improve memory and thinking skills in people with dementia. Participants will receive either transcranial direct current stimulation (tDCS) or transcranial alternating current stimulation (tACS), which are non-invasive brain stimulation techniques, at different frequencies, or a placebo treatment. The study will monitor changes in brain activity and balance to assess treatment effectiveness. It suits individuals aged 50 to 95 diagnosed with dementia but without other major cognitive or mood disorders. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new dementia treatments.

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 prior data suggests that this electrical stimulation technique is safe for older adults with dementia?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe for people with dementia. Studies indicate it is well-tolerated, with only mild side effects like tingling or itching, making it a non-invasive and painless option for brain stimulation.

For gamma transcranial alternating current stimulation (tACS), studies have found it safe and practical for use in dementia patients. Evidence suggests it can improve thinking abilities, and no major safety concerns have been reported.

Theta tACS, however, has shown mixed results. While researchers are studying its potential to help with thinking skills, some research suggests it might negatively affect memory when used on certain brain areas.

Overall, these treatments are being explored for their potential benefits and are considered safe in the context of controlled studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for dementia because they use electrical stimulation techniques, which offer a novel way to potentially enhance brain function. Unlike traditional medications that target chemical imbalances, Transcranial Alternating Current Stimulation (tACS) and Transcranial Direct Current Stimulation (tDCS) aim to directly influence brain activity by delivering mild electrical currents to specific brain regions. This approach could help improve cognitive function in dementia patients by promoting neural connectivity and brain plasticity. Moreover, these methods are non-invasive and can be customized for each patient, offering a promising alternative to existing drug therapies.

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

Research has shown that gentle electrical currents applied to the brain, such as transcranial direct current stimulation (tDCS), can enhance thinking abilities in people with dementia. In this trial, some participants will receive tDCS combined with brain exercises. Another method under study is gamma transcranial alternating current stimulation (tACS), which has shown promise in boosting memory and thinking skills in individuals with mild memory problems and Alzheimer's. Additionally, theta tACS, also being tested, may enhance thinking abilities in those experiencing cognitive decline. Overall, these electrical stimulation techniques may improve memory and thinking skills in dementia patients. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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.

Group VI: Bilateral DLPFC Experimental Treatment 1 Intervention

Applying the optimal tES over left and right DLPFC. First 30-min will target the left DLPFC similar to the other arms, and the second 30-min treatment will target tES to the right DLPFC (one electrode over right DLPFC and one electrode over contralateral supraorbital area).

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Published Research Related to This Trial

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]

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]

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 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]

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) 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]

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]

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, 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10862495/

The impact of gamma transcranial alternating current ... The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X23017412

The impact of gamma transcranial alternating current ... The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These ...

3. translationalneurodegeneration.biomedcentral.com translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-024-00423-y

Transcranial alternating current stimulation (tACS) at gamma ... Gamma tACS significantly improved performance in higher-level cognitive functions, in contrast to tDCS, although both induced changes in ...

4. researchprotocols.org researchprotocols.org/2022/4/e37282/

The Effect of Transcranial Alternating Current Stimulation ... Conclusions: We anticipate that transcranial alternating current stimulation will be a well-tolerated treatment, with no serious side effects ...

5. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.1068175/full

Transcranial alternating current stimulation combined with ... Gamma entrainment therapy can reduce the loss of functional brain connectivity and brain atrophy in AD patients, thereby improving cognitive function and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11210106/

Transcranial alternating current stimulation (tACS) at gamma ... We outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD.

7. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-024-01570-0

TRanscranial AlterNating current stimulation FOR patients ... This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity.

8. jdc.jefferson.edu jdc.jefferson.edu/cgi/viewcontent.cgi?article=1010&context=mossrehabfp

The Impact of Gamma Transcranial Alternating Current ... Although underpowered, this study is one of the first to demonstrate safety and feasibility of employing gamma tACS treatment in dementia ...

9. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.980636/full

Long-term gamma transcranial alternating current ... It is possible that 7 days of tACS cannot fundamentally interfere with AD in mice. Long-term gamma tACS can better reduce Aβ deposition and ...