Closed-Loop Neuromodulation for Alzheimer's Disease

Overseen By Joan Camprodon, MD, MPH, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Cancer, Cardiovascular disease, Stroke, others

Compensation: Varies

Number of Visits: 1

Duration: 1 session (30 minutes)

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The project is a placebo-controlled study that aims to use closed-loop transcranial alternating current stimulation (tACS) to study patients with symptoms of mild cognitive impairment which is likely due to Alzheimer's disease or another form of dementia (AD-MCI). Patients will undergo an EEG and complete some questionnaires and computer tasks during each study visit. The project has the following aims and hypotheses: 1.) To determine the impact of closed-loop 40 Hz tACS on the entrainment of natural gamma rhythms in patients with AD-MCI, 2.) To determine the impact of closed-loop 40 Hz tACS on cognitive performance in patients with AD-MCI, and 3.) To assess the relationship between baseline neurodegenerative burden and impact of tACS. \[exploratory\]

Do I need to stop my current medications for the trial?

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.

Is closed-loop neuromodulation using tACS safe for humans?

Transcranial alternating current stimulation (tACS) is generally considered safe, with most adverse effects being mild and disappearing soon after treatment. No persistent adverse events have been reported for tACS, but there are fewer safety studies compared to similar techniques, so ongoing research is needed to confirm its safety. ^{1 2 3 4 5}

How is the tACS treatment for Alzheimer's disease different from other treatments?

The tACS treatment is unique because it uses non-invasive electrical stimulation to modulate brain activity by targeting neural oscillations, which can improve memory and cognitive function in Alzheimer's patients. Unlike traditional drug treatments, tACS directly influences brain rhythms and can be customized for precision intervention. ^{3 6 7 8 9}

What data supports the effectiveness of the treatment tACS device for Alzheimer's Disease?

Research shows that transcranial alternating current stimulation (tACS) at gamma frequency can improve memory and brain function in people with Alzheimer's Disease by modulating brain rhythms and enhancing neural activity. Studies have found that tACS can improve cognitive performance and memory in both healthy adults and those with mild cognitive impairment or Alzheimer's Disease. ^{2 3 6 9 10}

Who Is on the Research Team?

Joan Camprodon, MD, PhD, MPH

Principal Investigator

MGH, Division of Neuropsychiatry and Neuromodulation

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 50-80 with mild cognitive impairment likely due to Alzheimer's, supported by AD biomarkers. It excludes those with brain lesions, acute medical conditions like cancer or heart failure, active major organ disorders, long-term substance abuse history, and contraindications to tACS such as scalp lesions or seizure history.

Inclusion Criteria

I have mild memory problems likely due to Alzheimer's, confirmed by tests.

I am between 50 and 80 years old.

I am a native English speaker.

Exclusion Criteria

I have a diagnosed brain lesion, such as a tumor.

I do not have any worsening or uncontrolled health conditions.

I have an active blood, kidney, lung, hormone, or liver disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive closed-loop transcranial alternating current stimulation (tACS) and undergo EEG, questionnaires, and computer tasks

1 session (30 minutes)

1 visit (in-person)

Follow-up

Participants are monitored for changes in cognitive performance and gamma power after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• tACS device

Trial Overview The study tests closed-loop transcranial alternating current stimulation (tACS) on patients with Alzheimer's-related mild cognitive impairment. It aims to see if tACS can synchronize natural brain rhythms and improve cognition. Participants will have EEGs and complete tasks during visits in this placebo-controlled study.

How Is the Trial Designed?

Group I: MCI Subjects Experimental Treatment 1 Intervention

Group II: Healthy Controls Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

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]

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]

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 direct current stimulation (tDCS) is generally considered safe, with most adverse effects being mild and temporary; however, some cases of persistent skin lesions and rare instances of mania or hypomania have been reported, particularly in patients with depression.

Transcranial alternating current stimulation (tACS) has fewer reported adverse events, and no persistent effects have been documented, but more research is needed to fully establish its safety compared to tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of tDCS and tACS: A review. Matsumoto, H., Ugawa, Y.[2020]

Transcranial alternating current stimulation (tACS) is a promising neurological intervention that can modulate perception, cognition, and consciousness by influencing oscillating neural activity.

tACS has unique advantages, such as the ability to entrain large groups of neurons and provide precise control over effects, making it a valuable tool for studying the neural basis of cognitive functions, but best practices must be followed for effective application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols. Tavakoli, AV., Yun, K.[2020]

Citations

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Neurocognitive, physiological, and biophysical effects of transcranial alternating current stimulation. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Home-based transcranial alternating current stimulation (tACS) in Alzheimer's disease: rationale and study design. [2023]

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

Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease. [2022]

5. United States 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tele-supervised home-based transcranial alternating current stimulation (tACS) for Alzheimer's disease: a pilot study. [2023]

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

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events of tDCS and tACS: A review. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting neural oscillations with transcranial alternating current stimulation. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols. [2020]