Transcranial Alternating Current Stimulation for Mild Cognitive Impairment

(tACS-MCI Trial)

Overseen By Dewi Clark, MHSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Acetylcholine inhibitors, Memantine, Anticonvulsants, Benzodiazepines

Disqualifiers: Major depressive disorder, Bipolar, Psychotic disorder, others

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

Compensation: Varies

Number of Visits: 12

Duration: 2 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new, non-invasive brain stimulation technique called transcranial alternating current stimulation (tACS) to determine its effectiveness in improving memory and thinking in people with mild cognitive impairment (MCI). tACS delivers a low electrical current to the brain, aiming to stimulate brain cells safely and without pain. Participants will undergo treatment sessions over two weeks and complete various assessments. The trial seeks individuals aged 60 or older who have been diagnosed with MCI and are willing to engage in consistent treatment and assessments. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for memory improvement.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to participate in this trial. Specifically, you cannot use acetylcholine esterase inhibitors, memantine, anticonvulsants (unless it's gabapentin or pregabalin with a stable dose for 4 weeks), or high doses of benzodiazepines.

What prior data suggests that this method is safe for people with Mild Cognitive Impairment?

Research shows that transcranial alternating current stimulation (tACS) is generally safe for people with memory and thinking problems. Studies have found that tACS can improve learning and memory in individuals with mild cognitive impairment (MCI) and Alzheimer's disease. Importantly, no serious side effects have been reported with tACS. Most people tolerate it well, undergoing the treatment without major issues. This non-invasive method uses low electrical currents to stimulate the brain, making it a low-risk option. Therefore, evidence suggests that participating in a trial involving tACS is a safe choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial alternating current stimulation (tACS) for mild cognitive impairment because it offers a unique non-invasive approach by directly modulating brain activity. Unlike traditional treatments like medications that often have systemic side effects, tACS uses weak electrical currents to target specific neural circuits, potentially enhancing cognitive functions more precisely. This method could provide a safer, more targeted option, minimizing side effects while potentially offering cognitive benefits faster than current pharmacological treatments.

What evidence suggests that transcranial alternating current stimulation is effective for mild cognitive impairment?

Research suggests that transcranial alternating current stimulation (tACS), a treatment participants in this trial may receive, might improve memory and thinking in people with Mild Cognitive Impairment (MCI). Studies have shown that tACS could benefit similar conditions like Alzheimer's disease, where it reduced harmful brain plaques and improved thinking skills after three weeks. The treatment sends a gentle electrical current through the brain, helping brain cells work better together. This improved coordination of brain activity might enhance memory and thinking skills. While still under study, early results are promising for those with MCI. Participants in this trial may also receive a sham version of tACS, serving as a control to evaluate the active treatment's effectiveness. ^{2 3 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 60 or above with Mild Cognitive Impairment (MCI) who can consent and communicate in English. They must not be using certain memory or mood-altering drugs, have a pacemaker, history of seizures, major psychiatric disorders, recent substance abuse, or active major depression.

Inclusion Criteria

Willingness to provide informed consent

Ability to read and communicate in English (with corrected vision and hearing, if needed)

I am 60 years old or older.

Exclusion Criteria

I am currently taking medication for memory problems.

Any contraindication to MRI or contraindication to tACS (e.g., cardiac pacemaker, acoustic device, history of seizures)

I use more than the equivalent of 2 mg/day of lorazepam.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete clinical and cognitive assessments and bloodwork at baseline

1 week

1 visit (in-person)

Treatment

Participants receive a 10-session course of tACS or sham-tACS, 5 days a week over 2 weeks

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Sham tACS
• Transcranial Alternating Current Stimulation

Trial Overview The study tests transcranial alternating current stimulation (tACS), a non-invasive brain stimulation method to improve working memory in MCI patients. Participants will receive tACS sessions at CAMH for up to 1.5 hours daily over two weeks and undergo assessments before and after treatment.

How Is the Trial Designed?

Group I: Active tACS Active Control 1 Intervention

After completing the Baseline testing at Visit 1 and N-back EEG at Visit 2, MCI participants randomized to the active condition will receive a 10-session course of tACS (Visits 4-13), followed by a follow-up assessment, post intervention, at Visit 14.

Group II: Sham tACS Placebo Group 1 Intervention

After completing the Baseline testing at Visit 1 and N-back EEG at Visit 2, MCI participants randomized to the sham condition will receive a 10-session course of sham-tACS (Visits 4-13), followed by a follow-up assessment, post intervention, at Visit 14.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Soterix Medical

Industry Sponsor

Trials

12

Recruited

410+

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]

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]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Gamma transcranial alternating current stimulation (tACS) is feasible and shows promise in improving episodic memory in individuals with amnestic mild cognitive impairment (aMCI), based on a study of 13 participants who underwent eight sessions.

The improvements in memory were linked to higher modeled electric fields from the tACS and changes in resting-state functional connectivity, suggesting that this noninvasive neurostimulation may enhance brain connectivity related to memory processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma neuromodulation improves episodic memory and its associated network in amnestic mild cognitive impairment: a pilot study. Jones, KT., Gallen, CL., Ostrand, AE., et al.[2023]

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 pilot study involving 30 older adults with multi-domain amnestic mild cognitive impairment (md-aMCI), transcranial alternating current stimulation (tACS) combined with cognitive control training (CCT) was found to be highly tolerable and feasible for at-home use.

Participants receiving prefrontal theta tACS showed significant improvements in attentional abilities within one week, suggesting that this neuromodulation technique may enhance cognitive control in individuals with md-aMCI, although further research with larger groups is necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing cognitive control in amnestic mild cognitive impairment via at-home non-invasive neuromodulation in a randomized trial. Jones, KT., Ostrand, AE., Gazzaley, A., et al.[2023]

In a study involving 20 patients with mild cognitive impairment (MCI), gamma-tACS (transcranial alternating current stimulation) demonstrated significant cognitive improvements compared to tDCS (transcranial direct current stimulation) and sham stimulation, particularly in tasks like the Stroop test and Trail-Making Test.

Gamma-tACS was found to enhance cognitive function by increasing beta brain activity, while tDCS did not show significant cognitive benefits and instead reduced slow-frequency brain activity, suggesting that tACS may be a more effective non-pharmacological treatment for MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tACS as a promising therapeutic option for improving cognitive function in mild cognitive impairment: A direct comparison between tACS and tDCS. Kim, J., Kim, H., Jeong, H., et al.[2021]

In a study involving 20 participants with mild cognitive impairment due to Alzheimer's disease, γ-tACS significantly improved memory performance, as shown by increased scores on the Rey auditory verbal learning test and face-name associations, compared to sham stimulation.

The γ-tACS also enhanced cholinergic transmission, indicated by increased short latency afferent inhibition measured with TMS, suggesting a potential mechanism for its memory-enhancing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Benussi, A., Cantoni, V., Cotelli, MS., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11712744/

Efficacy of Transcranial Alternating Current Stimulation ... Conclusion. Preliminary evidence suggests the potential efficacy of tACS for improving cognition in Alzheimer's disease patients. However, due to the limited ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X23017412

The impact of gamma transcranial alternating current ... TACS is being explored as a tool to improve cognition and memory in patient populations with mild cognitive impairment (MCI) and Alzheimer's disease (AD).

3. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/241884

Transcranial Alternating Current Stimulation on Cerebral ... Conclusions: Among patients with early AD, 77.5 Hz tACS led to a lower amyloid plaque burden and better cognitive performance at 3 weeks. In the ...

4. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-024-01570-0

TRanscranial AlterNating current stimulation FOR patients ... This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity.

5. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.087903

Efficacy of Transcranial Alternating Current Stimulation (tACS ... tACS can induce synchronization of neural networks leading to improvement in behavior and cognition. However, there's still controversy ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11306417/

Efficacy and Safety of Transcranial Magnetic Stimulation on ... The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06202872

Memory Enhancement Using Transcranial Alternating ... Transcranial alternating current stimulation (tACS) is a safe and patient-friendly non-invasive brain stimulation technique that serves as a potential candidate ...

8. researchprotocols.org researchprotocols.org/2022/4/e37282/

The Effect of Transcranial Alternating Current Stimulation ... Conclusions: We anticipate that transcranial alternating current stimulation will be a well-tolerated treatment, with no serious side effects ...