tDCS for Cognitive Impairment

(AIM Trial)

Overseen By Aprinda I Queen, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must not be taking: GABAergic, Glutamatergic, Calcium blockers, Sodium blockers

Disqualifiers: Neurological disorders, Seizures, Psychiatric disorders, Cancer, others

Compensation: Varies

Number of Visits: 3

Duration: 12 minutes per session, with sessions separated by at least two weeks

110 Participants Needed

Trial Summary

What is the purpose of this trial?

The current study is a mechanistic study to evaluate working memory gains from application of transcranial direct current stimulation (tDCS) in older adults with mild cognitive impairments (MCI) compared to cognitively healthy control

Will I have to stop taking my current medications?

If you are currently taking GABAergic or glutamatergic medications, or calcium or sodium channel blockers, you will need to stop, as these medications interfere with the study.

What data supports the effectiveness of the treatment tDCS for cognitive impairment?

Research suggests that transcranial direct current stimulation (tDCS) may help improve cognitive functions like memory and processing speed in conditions such as Alzheimer's disease and mild cognitive impairment. However, the evidence is not yet strong enough to make definitive conclusions, and more large-scale studies are needed to confirm its effectiveness. ^{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 serious adverse effects reported in over 33,200 sessions and 1,000 subjects, including vulnerable populations. Common side effects are mild and temporary, such as itching, tingling, and headaches. ^{6 7 8 9 10}

How is the treatment tDCS different from other treatments for cognitive impairment?

Transcranial Direct Current Stimulation (tDCS) is unique because it is a noninvasive method that uses a mild electrical current to stimulate the brain, unlike traditional drug treatments. It is being explored for its potential to improve cognitive function in conditions like Alzheimer's disease and mild cognitive impairment without the use of medication. ^{1 2 3 5 11}

Research Team

Aprinda I Queen, PhD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for older adults aged 60-95 with mild cognitive impairments (MCI). Participants must be able to attend training sessions, receive electrical stimulation, understand conversational voices, and have the motor skills to use a computer mouse. A Montreal Cognitive Assessment score of 18 or above is required.

Inclusion Criteria

I can use a computer mouse and click buttons without help.

Able to receive electrical stimulation

I am between 60 and 95 years old.

Exclusion Criteria

Terminal illness with life expectancy less than 12 months, as determined by physician

I have a brain tumor or a foreign object in my brain.

Contraindications to MRI recording (e.g., any kind of ferrous metallic stents or ferrous metal objects in the body, heart valve prosthesis, or other metal implants, claustrophobia, neurostimulation system, defibrillator, pacemaker, or other implanted device)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham tDCS stimulation to evaluate working memory gains

12 minutes per session, with sessions separated by at least two weeks

3 visits (in-person) per stimulation condition

Follow-up

Participants are monitored for changes in working memory performance and brain connectivity

4 weeks

Treatment Details

Interventions

• tDCS

Trial Overview The AIM Pilot Study is testing whether transcranial direct current stimulation (tDCS) can improve working memory in older adults with MCI. The study compares active tDCS against sham tDCS (a placebo-like treatment) to see if there's a real benefit from the intervention.

Participant Groups

Group I: Active tDCS Experimental Treatment 1 Intervention

AA neuroConn MR-safe 1x1 tDCS stimulator will be used to apply 12 minutes of 2.0 mA electrical current, with 30 seconds ramps up and 30 seconds ramps down. The electrical current will be applied by using two carbon rubber electrodes (one anode, one cathode) with added ten20 conductive paste. The electrode+paste will be affixed on the participant's scalp over the frontal cortices at F3 and F4 location (EEG 10-20 system). Inflow of current (anode) will occur at F4 location, and outflow of current will occur at F3 (cathode).

Group II: Sham tDCS Placebo Group 1 Intervention

Sham stimulation will be performed with the same 1x1 device. Participants will receive 2 mA of direct current stimulation for 30 seconds with 30 seconds ramps up and down. This provides the tingling and prickling sensation on the scalp associated with tDCS while prevent delivering sufficient current (12 minutes) to penetrate the skull and stimulate the brain. Prep in sham conditions will be identical to active stimulation conditions. For each stimulation condition (active, sham), each participant will perform three runs of N-back working memory task (baseline/pre-stimulation, during stimulation, and after/post-stimulation) as detailed below. Sham efficacy will be evaluated as a direct comparison in N-back performance and connectivity results in active group versus sham group.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

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]

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]

Anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex significantly improved cognitive tasks related to processing speed, selective attention, and planning in five older adults with mild cognitive impairment (MCI).

The study suggests that combining tDCS with cognitive stimulation programs may enhance cognitive performance in individuals with MCI, but further research is needed to explore long-term effects and practical applications in daily life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct Current Stimulation on the Cognitive Functions in Older Adults with Mild Cognitive Impairment: A Pilot Study. Cruz Gonzalez, P., Fong, KNK., Brown, T.[2022]

Transcranial direct current stimulation (tDCS) has shown potential to improve cognitive functions such as processing speed, working memory, and executive functions in patients with mood disorders and schizophrenia, based on a systematic review of 41 studies.

The effects of tDCS on cognitive functioning and memory in Alzheimer's disease and mild cognitive impairment are less clear, with evidence being inconclusive or weak, highlighting the need for standardized protocols in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation and Cognition in Neuropsychiatric Disorders: Systematic Review of the Evidence and Future Directions. Ciullo, V., Spalletta, G., Caltagirone, C., et al.[2022]

This study will evaluate the safety and efficacy of transcranial direct current stimulation (tDCS) combined with cognitive tasks in patients with neurocognitive disorders, using a randomized controlled trial design with 92 participants (46 per group).

The primary outcome will be measured by changes in cognitive function using the Alzheimer Disease Assessment Scale, with additional assessments for depressive symptoms and quality of life, providing a comprehensive evaluation of tDCS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of multisession transcranial direct current stimulation as an augmentation to cognitive tasks in patients with neurocognitive disorders in Japan: a study protocol for a randomised controlled trial. Inagawa, T., Yokoi, Y., Yamada, Y., et al.[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]

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]

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]

Microdermabrasion significantly reduced skin resistance by about 32%, allowing for higher doses of transcranial direct current stimulation (tDCS) without increasing skin sensations or device limitations.

The study found that while microdermabrasion increased perceived sensations slightly when not combined with sonication, overall, it enabled safer and more effective delivery of tDCS by lowering the voltage needed to achieve the same current.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. Chhatbar, PY., Liu, S., Ramakrishnan, V., et al.[2023]

Transcranial direct current stimulation (tDCS) is generally considered safe, with mild and transient adverse effects reported in clinical trials, but the frequency and relationship of these effects with clinical variables remain unclear due to selective reporting bias.

Out of 209 studies reviewed, 117 mentioned adverse effects, with common issues like itching and tingling reported more frequently in the active tDCS group, although these differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Brunoni, AR., Amadera, J., Berbel, B., et al.[2022]

Transcranial direct current stimulation (tDCS) was found to be safe and well-tolerated in a study involving 20 patients with mild or major neurocognitive disorders, with an attrition rate of 0% and no serious adverse events reported.

However, the study did not find any statistically significant improvements in cognitive functioning when comparing the active tDCS group to the sham group, indicating that tDCS may not enhance cognitive performance in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study. Inagawa, T., Yokoi, Y., Narita, Z., et al.[2022]

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. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct Current Stimulation on the Cognitive Functions in Older Adults with Mild Cognitive Impairment: A Pilot Study. [2022]

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

Transcranial Direct Current Stimulation and Cognition in Neuropsychiatric Disorders: Systematic Review of the Evidence and Future Directions. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effects of multisession transcranial direct current stimulation as an augmentation to cognitive tasks in patients with neurocognitive disorders in Japan: a study protocol for a randomised controlled trial. [2021]

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

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

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. England pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. [2023]

10. England pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study. [2022]