Electrical Stimulation for Learning and Memory in Alzheimer's and Primary Progressive Aphasia

Overseen by Kyrana Tsapkini, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Johns Hopkins University

Disqualifiers: Neurological disease, Hearing loss, Visual acuity loss, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for Alzheimer's patients using a gentle electrical brain stimulation combined with memory exercises. It aims to help those who struggle with memory or language by improving brain cell connections. Transcutaneous electrical nerve stimulation (TENS) has shown positive effects on memory, verbal fluency, and affective behavior in Alzheimer's patients in previous studies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for Alzheimer's Disease?

Research shows that transcranial direct current stimulation (tDCS) can improve memory and cognitive function in people with Alzheimer's disease. Studies suggest that tDCS is a safe and promising non-drug treatment that may help slow down cognitive decline in Alzheimer's patients. ^{1 2 3 4 5}

Is non-invasive brain stimulation safe for humans?

Transcranial Direct Current Stimulation (tDCS), including its high-definition version (HD-tDCS), is generally considered safe in humans, with no serious adverse effects reported in over 33,200 sessions across various populations, including the elderly. However, some studies suggest potential risks, so caution is advised. ^{5 6 7 8 9}

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

Active HD-tDCS is a non-invasive brain stimulation technique that uses small, high-definition electrodes to deliver electrical currents to specific brain areas, which may improve cognitive function in Alzheimer's patients. Unlike traditional drug treatments, it does not involve medication and is designed to be more comfortable than conventional tDCS methods. ^{1 2 4 5 10}

Research Team

Kyrana Tsapkini, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for right-handed individuals aged 50-75 with a high-school education, proficient in English, and diagnosed with Alzheimer's Disease or Primary Progressive Aphasia. They must have cognitive impairment consistent with AD biomarkers but no history of brain injuries like stroke or tumors.

Inclusion Criteria

I have a specific type of speech difficulty due to Alzheimer's.

Participants will be diagnosed with a certain type of dementia called PPA or early dementia by specialized clinics using tests to measure language, memory, and brain imaging. The doctors will also use two new tests to accurately identify the specific type of PPA.

Have you completed a high-school level education?

Exclusion Criteria

I have had a previous brain injury.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive active HD-tDCS + Word List Learning Intervention (WordLLI) or Sham + WordLLI for 2 weeks, with 5 learning sessions per week

2 weeks

10 visits (in-person)

Washout

A 3-month stimulation-free washout period between the two treatment periods

3 months

Treatment Period 2

Participants receive the alternate condition (active HD-tDCS + WordLLI or Sham + WordLLI) for 2 weeks, with 5 learning sessions per week

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with evaluations at 1 month and 3 months post each treatment period

6 months

4 visits (2 in-person, 2 virtual)

Treatment Details

Interventions

• Active HD-tDCS (Electrical Stimulation)
• Sham (Electrical Stimulation)
• Word List Learning Intervention (WordLLI) (Behavioural Intervention)

Trial Overview The study tests if electrical brain stimulation (HD-tDCS) combined with a Word List Learning Intervention can improve verbal learning in typical and atypical Alzheimer's patients by comparing active treatment to sham (placebo). It also examines changes in brain connectivity and neurotransmitter levels.

Participant Groups

Group I: Sham+word intervention then active HD-tDCS+word intervention Experimental Treatment 3 Interventions

Participants will receive Sham + Word List Learning Intervention (WordLLI) and then active HD-tDCS + WordLLI after a three-month washout period.

Group II: Active HD-tDCS+word intervention then Sham+word intervention Experimental Treatment 3 Interventions

Participants will receive active HD-tDCS + Word List Learning Intervention (WordLLI) and then receive Sham + WordLLI after a three-month washout period.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

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 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 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]

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]

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]

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) 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]

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]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes up to 4 mA was well tolerated by 292 older adults, with no safety-related adverse events reported and mostly mild sensations experienced during sessions.

The study demonstrated effective blinding for both participants and researchers, indicating that the sham stimulation was convincing, which supports the use of higher amplitudes for potentially greater therapeutic effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. El Jamal, C., Harrie, A., Rahman-Filipiak, A., et al.[2023]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) is a safe and well-tolerated method for non-invasive brain stimulation, even when using a 2 mA current for 22 minutes.

Using a 6% benzocaine topical numbing agent significantly reduces discomfort during HD-tDCS sessions, which can improve the quality of sham-controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced discomfort during high-definition transcutaneous stimulation using 6% benzocaine. Guleyupoglu, B., Febles, N., Minhas, P., et al.[2021]

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

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

3. 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]

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

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

5. 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]

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

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

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

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

8. 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]

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

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Reduced discomfort during high-definition transcutaneous stimulation using 6% benzocaine. [2021]