tDCS for Alzheimer's Dementia

(tTED Trial)

Overseen By Gifty Asare, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Anticonvulsants, Benzodiazepines

Disqualifiers: Delirium, Acute medical condition, others

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

Compensation: Varies

Number of Visits: 8

Duration: 2 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to manage agitation and aggression in people with Alzheimer's dementia. It uses transcranial direct current stimulation (tDCS), which involves placing electrodes on the head to gently stimulate the brain. The goal is to determine if this approach can ease neuropsychiatric symptoms, which affect many with Alzheimer's. Participants should have Alzheimer's with noticeable agitation or aggression and must be stable on any current medication for at least a week. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve the quality of life for those with Alzheimer's.

Will I have to stop taking my current medications?

The trial requires that if you are taking medication for neuropsychiatric symptoms, your dose should be stable for at least 1 week. However, if you are taking anticonvulsants or benzodiazepines at a dose that interferes with the study, you may need to stop or adjust them.

What prior data suggests that this method is safe for treating agitation in Alzheimer's dementia?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe. Studies have found that using tDCS at 2 mA for 20 to 30 minutes can safely improve thinking skills in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants in these studies did not report major side effects, indicating that tDCS is a safe option for enhancing cognitive function related to Alzheimer's.

While minor side effects like tingling or itching at electrode sites can occur, these are usually mild and temporary. Overall, the evidence supports tDCS as a promising and safe method for managing Alzheimer's symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about tDCS for Alzheimer's dementia because it offers a non-invasive approach to potentially improve cognitive function. Unlike medications like donepezil or memantine, which work by altering neurotransmitter activity, tDCS uses electrical currents to directly stimulate specific brain regions, such as the frontal lobes. This technique might offer a novel way to enhance brain activity and improve symptoms without the side effects commonly associated with traditional drugs. Additionally, tDCS could show results quickly, as it is administered daily over a short period, making it a promising option for faster symptom management.

What evidence suggests that tDCS is effective for treating agitation in Alzheimer's dementia?

Research has shown that transcranial direct current stimulation (tDCS) can improve symptoms in people with Alzheimer's disease. Studies have found that multiple tDCS sessions significantly boost overall thinking abilities in older adults with Alzheimer's. Further research suggests that tDCS may aid specific memory tasks, such as learning and remembering. Early findings indicate that tDCS might effectively manage symptoms like agitation in Alzheimer's patients. This trial will compare active tDCS with sham tDCS to evaluate its effectiveness. These results offer hope for tDCS as a treatment option. ^{2 5 6 7 8}

Who Is on the Research Team?

Sanjeev Kumar, MD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for individuals aged 50 or older with Alzheimer's dementia who experience agitation. They must have a stable dose of neuropsychiatric medication if they're taking any, and cannot be on certain drugs like anticonvulsants or benzodiazepines that interfere with the study. Participants need informed consent and a support person to attend appointments.

Inclusion Criteria

Able and willing to provide informed consent

Healthy comparator participants:

I am 50 years old or older.

Exclusion Criteria

Any contraindication to TMS

Any contraindication to TMS or tDCS

I have a psychiatric condition, but it's not dementia, affecting my health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Clinical and cognitive assessments, as well as TMS EEG to assess cortical inhibition, are performed at baseline

1 week

1 visit (in-person)

Treatment

Participants receive a 2-week course of active/sham cathodal tDCS to the frontal brain region in a double-blind randomized control design

2 weeks

5 visits per week (in-person or virtual)

Post-Treatment Assessment

Assessment of cortical inhibition and clinical symptoms using measures identical to baseline

1 week

1 visit (in-person or virtual)

Follow-up

Participants are monitored for changes in clinical symptoms and cortical inhibition 2 weeks after the last tDCS session

2 weeks

1 visit (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• tDCS

Trial Overview

The study tests non-invasive brain stimulation methods (TMS-EEG and tDCS) to understand and treat agitation in Alzheimer's dementia. It aims to explore the underlying mechanisms of these symptoms using magnetic stimulation combined with EEG, as well as assess the effectiveness of tDCS treatment.

How Is the Trial Designed?

Group I: Active tDCS Experimental Treatment 1 Intervention

The direct current will be delivered at 2 mA intensity via rubber electrodes in saline- soaked sponges for 30 min per day for 2 weeks, 5 days/week. Inhibitory stimulation will be delivered to the frontal lobes.

Group II: sham tDCS Placebo Group 1 Intervention

Sham tDCS will use the same parameters except that the device will automatically turn off after a certain duration.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

BrightFocus Foundation

Collaborator

Trials

5

Recruited

430+

Published Research Related to This Trial

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 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]

This study protocol aims to evaluate the safety and clinical effects of transcranial direct current stimulation (tDCS) on depression in Alzheimer's patients aged over 65, addressing a gap in research for older adults.

The trial is designed as a randomized controlled study with blinding, comparing active tDCS to a sham treatment, and will assess participants' depression and cognitive function at multiple time points to determine the intervention's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial. Narita, Z., Yokoi, Y.[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]

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]

In a study involving 36 patients with Alzheimer's disease, multisite anodal transcranial direct current stimulation (tDCS) combined with cognitive stimulation significantly delayed cognitive decline compared to a sham treatment, as measured by the ADAS-cog scale.

The active tDCS+CS group showed greater changes in EEG coherence, indicating enhanced brain activity, which correlated with improvements in cognitive performance, suggesting that this combined approach may effectively modulate brain function in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of multisite anodal transcranial direct current stimulation combined with cognitive stimulation in patients with Alzheimer's disease and its neurophysiological correlates: A double-blind randomized clinical trial. Andrade, SM., Machado, DGDS., Silva-Sauerc, LD., et al.[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) 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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