tDCS for Alzheimer's Dementia

(tTED Trial)

Overseen by Sanjeev Kumar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Anticonvulsants, Benzodiazepines

Disqualifiers: Delirium, Acute medical condition, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Agitation and aggression impose a tremendous burden on the individuals living with dementia, their families, caregivers, and healthcare systems. Neuropsychiatric symptoms of dementia (NPS) affect up to 80% of patients with Alzheimer's dementia (AD). The mechanisms of agitation in AD are poorly understood and the current interventions are only modestly effective while having serious adverse effects. In this study, the investigators propose to assess the mechanisms and treatment of neuropsychiatric symptoms in AD with the use of non-invasive, brain stimulation approaches. By applying magnetic stimulation to the surface of the head (transcranial magnetic stimulation - TMS) combined with electroencephalography (EEG), the investigators will be able to study the mechanisms of agitation and advance our understanding of AD. Further, the investigators will evaluate if transcranial direct current stimulation (tDCS) is effective to treat agitation dementia.

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 data supports the effectiveness of the treatment tDCS for Alzheimer's dementia?

Research suggests that transcranial direct current stimulation (tDCS) may help improve or slow down cognitive decline in Alzheimer's patients. Studies have shown that tDCS can enhance memory and cognitive performance, especially when combined with cognitive exercises. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Transcranial direct current stimulation (tDCS) is generally considered safe for humans, with no reports of serious adverse effects or irreversible injury in over 33,200 sessions across various populations, including the elderly and those with mood disorders. ^{1 6 7 8 9}

How is the treatment tDCS different from other treatments for Alzheimer's disease?

Transcranial Direct Current Stimulation (tDCS) is unique because it is a noninvasive method that uses electrical currents to stimulate the brain, unlike traditional drug treatments. It aims to improve or delay cognitive decline in Alzheimer's patients by directly targeting brain activity, offering a non-drug alternative for managing the condition. ^{1 2 3 4 7}

Research Team

Sanjeev Kumar, MD

Principal Investigator

Centre for Addiction and Mental Health

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• tDCS (Brain Stimulation)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

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

2. Switzerland 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. [2022]

3. 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]

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

Transcranial direct current stimulation improves recognition memory in Alzheimer disease. [2022]

5. France 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. [2022]

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

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

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

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis. [2020]

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

Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial. [2022]

9. 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]