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

Overseen By Kyrana Tsapkini, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

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

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

Compensation: Varies

Number of Visits: 24

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with Alzheimer's disease (AD) using a non-invasive brain stimulation technique called transcranial Direct Current Stimulation (tDCS). The researchers aim to determine if tDCS can enhance memory and language skills by strengthening brain connections, particularly when combined with a word-learning exercise. The study includes two groups: one receives the real treatment first, while the other begins with a placebo (inactive treatment) before switching. Suitable candidates for this trial are English-speaking, right-handed individuals with Alzheimer's symptoms related to memory or language issues, confirmed by specific medical tests. As an unphased trial, this study presents a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for Alzheimer's.

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 prior data suggests that this non-invasive brain stimulation is safe for Alzheimer's patients?

Research has shown that Transcranial Direct Current Stimulation (tDCS) is generally safe and well-tolerated. Studies have found that individuals using tDCS, including those with Alzheimer's Disease (AD), typically do not experience serious side effects. Most report either no sensation or only mild tingling during treatment sessions. These studies have not observed any safety-related problems.

This safety profile is crucial because tDCS is a non-invasive treatment, meaning it doesn't involve surgery or entering the body. The treatment uses a gentle electrical current applied to the scalp to enhance brain function, especially when combined with activities like language or memory exercises.

Overall, tDCS is considered a safe option for individuals with AD, with the potential to help slow memory and thinking problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for Alzheimer's, which often involve medications that target neurotransmitters, active HD-tDCS (High-Definition Transcranial Direct Current Stimulation) is a non-invasive brain stimulation technique. Researchers are excited about this method because it uses electrical currents to potentially enhance brain function and cognitive abilities directly, which is a novel approach compared to traditional drugs. Additionally, this method, combined with word learning interventions, might offer a dual benefit by not only stimulating the brain but also engaging it in cognitive exercises, potentially leading to more significant improvements in memory and learning.

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

This trial will compare the effects of active transcranial direct current stimulation (tDCS) with a sham (inactive) version, both combined with a Word List Learning Intervention (WordLLI), on cognitive abilities in people with Alzheimer's disease (AD). Studies have shown that tDCS, a type of brain stimulation, can improve thinking and memory in people with AD. Research suggests that applying tDCS twice a day might enhance cognitive abilities in those with AD. A review of several studies found that people with AD showed more improvement with tDCS than those with mild cognitive impairment (MCI) or other types of dementia. However, some studies did not find a significant difference between real tDCS and a sham version immediately after treatment. These mixed results indicate that while tDCS shows promise, its effectiveness can vary, and more research is needed to understand its full benefits for AD. ^{1 5 6 7 8}

Who Is on the Research Team?

Kyrana Tsapkini, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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 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]

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]

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]

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]

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) 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]

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) 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]

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