Noninvasive Brain Stimulation for Mild Cognitive Impairment

Overseen By David Ziegler, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Antidepressants, Antianxiety

Disqualifiers: Neurological, Psychiatric, Seizures, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new noninvasive brain stimulation treatment can improve thinking skills and overall well-being in people with mild cognitive impairment (MCI). The study tests a device called transcranial alternating current stimulation (tACS) alongside one of two digital brain exercises. It seeks participants who are comfortable moving around, speak English fluently, and have mild cognitive issues but no major brain or mental health disorders. The trial is unsuitable for those with metal implants or devices like pacemakers. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could enhance cognitive health.

Will I have to stop taking my current medications?

You cannot participate in the trial if you are taking anti-depressants or anti-anxiety medications. The protocol does not specify about other medications, so it's best to discuss your specific situation with the trial coordinators.

What prior data suggests that this noninvasive neurostimulation device is safe for adults with mild cognitive impairment?

Research has shown that non-invasive brain stimulation, such as transcranial alternating current stimulation (tACS), is generally safe and well-tolerated. Studies have found that tACS is painless and participants manage it well. It is also more affordable than other treatments. For individuals with mild cognitive impairment, tACS has been used to improve thinking skills without serious side effects.

In this trial, both treatment options, MediTrain and Worder, use a type of non-invasive brain stimulation. Past research on similar methods highlights their safety and potential to enhance cognition in individuals with conditions like mild cognitive impairment. Importantly, these studies have reported no major safety concerns.

For those considering joining a trial, this indicates a history of safety in similar situations. However, as with any treatment, it is important to monitor comfort and any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for mild cognitive impairment because they use noninvasive neurostimulation, offering a new approach compared to standard medications like cholinesterase inhibitors or memantine. Unlike other treatments that often rely on pharmaceuticals to manage symptoms, these devices—MediTrain and Worder—utilize gentle brain stimulation to potentially enhance cognitive function without the side effects associated with drugs. This innovative method targets brain activity directly, aiming to improve memory and thinking skills more naturally and safely.

What evidence suggests that this noninvasive neurostimulation device is effective for mild cognitive impairment?

Studies have shown that non-invasive brain stimulation, such as transcranial alternating current stimulation (tACS), can enhance thinking skills in people with mild cognitive impairment (MCI). Research indicates that tACS can improve attention and memory, which are often affected in MCI. In this trial, participants in the MediTrain group will receive a combination of brain stimulation and focused-attention meditation, which has shown promise in enhancing cognitive abilities. Meanwhile, participants in the Worder group will receive non-invasive brain stimulation, which reviews suggest is both effective and safe for improving thinking skills in people with MCI. Overall, these treatments aim to help people with MCI by enhancing brain function and improving memory and attention. ^{6 7 8 9 10}

Who Is on the Research Team?

David Ziegler, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults with mild cognitive impairment (MCI), a condition where people have slight but noticeable and measurable decline in cognitive abilities, including memory and thinking skills. Specific eligibility criteria are not provided.

Inclusion Criteria

comfortably ambulatory healthy physical condition normal or corrected to normal visual auditory acuity fluency in spoken English Between 60-85 years old No neurological or psychiatric disorders No substance abuse Not taking anti-depressants Not taking anti-anxiety medication No history of seizures No color blindness No glaucoma No macular degeneration No amblyopia (lazy eye) No strabismus (cross eyed) Aneurysm clip(s) No Cardiac pacemaker No Implanted cardioverter defibrillator (ICD) No Electronic implant or device No Magnetically-activated implant or device No Neurostimulation system No Spinal cord stimulator No Internal electrodes or wires No Bone growth/bone fusion stimulator No Cochlear, otologic, or other ear implant No Insulin or other infusion pump No Implanted drug infusion device No type of prosthesis (eye, penile, etc.) No Heart valve prosthesis No Eyelid spring or wire No Artificial or prosthetic limb No Metallic stent, filter, or coil No Shunt (spinal or intraventricular) No Vascular access port and/or catheter No Radiation seeds or implants No Swan-Ganz or thermodilution catheter No Medication patch (Nicotine, Nitroglycerine) No metallic fragment or metallic foreign body in/on the body that can not be removed No Wire mesh implant No Tissue expander (e.g., breast) No Surgical staples, clips, or metallic sutures No Joint replacement (hip, knee, etc.) No Bone/joint pin, screw, nail, wire, plate, etc. No IUD, diaphragm, or pessary No Dentures or partial plates that can not be removed No Tattoo or permanent makeup No Body piercing jewelry No Claustrophobi

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination treatment of non-invasive brain stimulation (tACS) and one of two digital cognitive interventions

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Immediate follow-up

What Are the Treatments Tested in This Trial?

Interventions

• noninvasive neurostimulation device

Trial Overview

The study tests if noninvasive brain stimulation (tACS) combined with digital cognitive exercises (MediTrain or Worder) can improve cognition and wellbeing in MCI patients. Participants will also use wrist-worn sensors to monitor various health metrics.

How Is the Trial Designed?

Group I: Worder Experimental Treatment 3 Interventions

Group II: MediTrain Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Transcranial alternating current stimulation (TACS) has demonstrated significant efficacy in improving symptoms of depression, with a standardized mean difference (SMD) of 1.14, indicating a strong positive effect compared to sham stimulation in patients.

TACS also showed a notable improvement in cognitive function among patients with psychiatric disorders, with an SMD of 0.60, suggesting it may enhance cognitive abilities in both patients and healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation and its effects on cognition and the treatment of psychiatric disorders: a systematic review and meta-analysis. Lee, ARYB., Yau, CE., Mai, AS., et al.[2022]

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 alternating current stimulation (tACS) shows promise in improving cognitive functioning in older adults, with 7 out of 9 studies on cognitively intact individuals reporting cognitive improvements after stimulation.

However, there is significant variability in study methodologies and outcomes, highlighting the need for standardized protocols and a better understanding of how tACS affects different populations, particularly regarding dosing and physiological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of tACS Effects on Cognitive Functioning in Older Adults Across the Healthy to Dementia Spectrum. Kraft, JD., Hampstead, BM.[2023]

Transcranial alternating current stimulation (tACS) has shown promising effects in improving cognitive and memory processes in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suggesting its potential as a therapeutic tool.

While tACS appears to enhance brain function and cognition, further research is needed to fully understand its effects on the underlying pathophysiology of MCI and AD, as well as its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of gamma transcranial alternating current stimulation (tACS) on cognitive and memory processes in patients with mild cognitive impairment or Alzheimer's disease: A literature review. Nissim, NR., Pham, DVH., Poddar, T., 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]

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]

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]

The study evaluates the efficacy and safety of transcranial alternating current stimulation (tACS) in treating major depressive disorder (MDD) over 8 weeks, involving 92 drug-naive patients who received either active or sham stimulation.

The primary outcome is the remission rate measured by the Hamilton depression rating scale, with the study aiming to demonstrate that tACS can effectively reduce depression symptoms with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial. Wang, HX., Wang, K., Zhang, WR., et al.[2023]

Repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS) have been shown to significantly enhance cognitive function in patients with Alzheimer's disease (AD), with rTMS also providing beneficial long-term effects.

The study recommends using high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) as a probably effective treatment for AD, while anodal tDCS over the same area is considered possibly effective, based on a meta-analysis of 32 studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is non-invasive brain stimulation effective for cognitive enhancement in Alzheimer's disease? An updated meta-analysis. Šimko, P., Kent, JA., Rektorova, I.[2023]

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