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

Trial Summary

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 data supports the effectiveness of the treatment Transcranial Alternating Current Stimulation for Mild Cognitive Impairment?

Research shows that transcranial alternating current stimulation (tACS) can improve cognitive function in people with mild cognitive impairment (MCI). In one study, tACS was found to enhance certain cognitive tests more effectively than another similar treatment, tDCS, and increased brain activity related to cognitive function. ^{1 2 3 4 5}

Is transcranial alternating current stimulation (tACS) safe for humans?

Transcranial alternating current stimulation (tACS) is generally considered safe for humans, with no serious adverse events reported in over 18,000 sessions. Mild side effects like headaches and skin sensations are possible, but serious harm is unlikely at low intensities used in studies. ^{1 2 3 6 7}

How does transcranial alternating current stimulation (tACS) differ from other treatments for mild cognitive impairment?

Transcranial alternating current stimulation (tACS) is unique because it uses non-invasive electrical currents to stimulate the brain, specifically targeting cognitive functions by increasing brain activity in certain areas. Unlike other treatments, tACS can be administered at home and has shown promise in improving cognitive functions like memory and attention in mild cognitive impairment, making it a novel option compared to traditional drug therapies. ^{1 2 4 5 8}

What is the purpose of this trial?

This study is looking at a new non-invasive brain stimulation methods called transcranial alternating current stimulation (tACS) to see if it can improve working memory and thinking processes in people with Mild Cognitive Impairment (MCI). tACS is a low-risk, non-painful, low electrical current that circulates through the brain of awake participants and stimulates their brain cells. Participants must be 60 years of age and have a diagnosis of mild cognitive impairment. Participants will undergo treatment sessions that range from 1 to 1.5 hours at CAMH, 5 days a week, over a total of 2 weeks. In addition, participants will complete clinical and cognitive assessments and bloodwork at baseline and again after treatment.

Research Team

Sanjeev Kumar, MD

Principal Investigator

Centre for Addiction and Mental Health

Eligibility Criteria

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.

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

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

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

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

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

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

Gamma neuromodulation improves episodic memory and its associated network in amnestic mild cognitive impairment: a pilot study. [2023]

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

Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

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

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

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

Enhancing cognitive control in amnestic mild cognitive impairment via at-home non-invasive neuromodulation in a randomized trial. [2023]