Vagus Nerve Stimulation for Alzheimer's Disease

Overseen By Elizabeth Riley, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Cornell University

Disqualifiers: Brain injury, Epilepsy, Concussion, others

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

Compensation: Varies

Number of Visits: 2

Duration: 15-45 minutes

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The locus coeruleus (LC) has recently been identified as one of the earliest sites of damage in AD with pathological lesions appearing as early as the mid-20s. In this study, the investigators use a variety of techniques including structural MRI, functional MRI, pupillometry, and transcutaneous vagus nerve stimulation to assess the health of the LC and its relation to easily measurable peripheral variables.

Will I have to stop taking my current medications?

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 vagus nerve stimulation safe for humans?

Vagus nerve stimulation, including the non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe with mild and temporary side effects like ear pain, headache, and tingling. Serious side effects are rare, and the non-invasive methods improve safety by avoiding surgical risks. ^{1 2 3 4 5}

How does vagus nerve stimulation differ from other treatments for Alzheimer's disease?

Vagus nerve stimulation (VNS) is unique because it involves stimulating the vagus nerve, which can enhance cognitive function by improving brain connectivity and cerebral blood flow. Unlike traditional Alzheimer's treatments that often focus on medications, VNS is a non-drug therapy that has shown promise in improving cognition in conditions like epilepsy and depression, and now is being explored for Alzheimer's disease. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment t-VNS transcutaneous auricular vagus nerve stimulator for Alzheimer's Disease?

Research shows that vagus nerve stimulation (VNS) has been used successfully for epilepsy and depression, and studies suggest it may also help improve thinking and memory in Alzheimer's patients. Non-invasive VNS, like t-VNS, has shown potential benefits for cognitive performance and healthy aging, making it a promising treatment for Alzheimer's. ^{4 6 7 8 10}

Are You a Good Fit for This Trial?

This trial is for individuals with Alzheimer's Disease. It focuses on early damage in a brain area called the locus coeruleus (LC). Participants should be able to undergo MRI scans and vagus nerve stimulation without any issues.

Inclusion Criteria

Able to speak and understand English

Willing and able to use a keyboard and mouse

I can have a 90-minute MRI scan at Cornell.

Exclusion Criteria

I have a moderate or severe brain injury.

Recent concussion

Colorblindness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including MRI, blood pressure testing, and cognitive tasks

1 day

1 visit (in-person)

Treatment

Participants receive short-duration vagus nerve stimulation while engaging in cognitive tasks

15-45 minutes

1 visit (in-person)

Follow-up

Participants are monitored for changes in cognitive performance and physiological responses

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• t-VNS transcutaneous auricular vagus nerve stimulator

Trial Overview The study tests if stimulating the vagus nerve through the skin (using t-VNS) can affect LC health and cognitive function. Techniques like MRI, functional MRI, and pupillometry are used to measure outcomes.

How Is the Trial Designed?

Group I: Cornell University Experimental Treatment 1 Intervention

Short-duration (less than an hour) vagus nerve stimulation will be delivered while participants engage in cognitive tasks and games. This study also includes a 90-minute MRI, blood pressure testing, saliva collection for genetic analysis, sensory testing, and blood pressure/heart rate measurement.

Who Is Running the Clinical Trial?

Cornell University

Lead Sponsor

Trials

179

Recruited

14,090,000+

Published Research Related to This Trial

Vagus nerve stimulation (VNS) was well tolerated over one year in a study of 17 patients with Alzheimer's disease, showing promising cognitive-enhancing effects with 41.2% of patients improving on the ADAS-cog scale.

After one year, there was no significant decline in mood, behavior, or quality of life, suggesting that VNS may be a safe long-term treatment option for cognitive decline in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in patients with Alzheimer's disease: Additional follow-up results of a pilot study through 1 year. Merrill, CA., Jonsson, MA., Minthon, L., et al.[2022]

In a pilot study involving 10 patients with Alzheimer's disease, vagus nerve stimulation (VNS) showed a positive effect on cognitive function, with 70% of patients improving on the Alzheimer's Disease Assessment Scale (ADAS-cog) and 90% on the Mini-Mental State Examination (MMSE) after 3 months.

VNS was well tolerated by patients, with only mild and transient side effects reported, suggesting it is a safe intervention for cognitive enhancement in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. Sjögren, MJ., Hellström, PT., Jonsson, MA., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved visual memory performance in a study of 60 healthy individuals aged 18 to 24, compared to a control group that did not receive taVNS.

Despite the positive effects on visual memory, taVNS did not show a significant impact on fatigue levels, indicating that while it may enhance cognitive function, it does not alleviate feelings of tiredness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of transcutaneous auricular vagus nerve stimulation on visual memory performance and fatigue. Yıldız, R., Özden, AV., Nişancı, OS., et al.[2023]

Vagus nerve stimulation (VNS) has been effectively used to treat conditions like intractable epilepsy and treatment-resistant depression, and new non-invasive methods like transcutaneous VNS (t-VNS) provide similar benefits without the risks associated with surgery.

t-VNS shows promise for improving cognitive function and neurocardiovascular stability, particularly in aging populations, by enhancing cerebral blood flow and regulating the body's parasympathetic responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"The Wandering Nerve Linking Heart and Mind" - The Complementary Role of Transcutaneous Vagus Nerve Stimulation in Modulating Neuro-Cardiovascular and Cognitive Performance. Dolphin, H., Dukelow, T., Finucane, C., et al.[2022]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) showed promising results in two patients with structural focal epilepsy, leading to seizure freedom in one patient after 4 weeks and significant reduction in seizures for the other after 20 weeks.

Both patients experienced improved quality of life with no significant adverse events reported, suggesting that taVNS could be a safe and effective treatment option for individuals with focal epilepsy and preserved cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report. Shiraishi, H., Egawa, K., Murakami, K., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) shows potential as a treatment for disorders of consciousness, particularly in patients with a minimally conscious state (MCS), as it significantly alters brain activity measured by EEG.

In patients with MCS, taVNS led to notable changes in both delta and beta brain wave energy across multiple regions, suggesting it may enhance brain connectivity and promote awakening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. Yifei, W., Yi, Y., Yu, W., et al.[2023]

Citations

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

Vagus nerve stimulation in patients with Alzheimer's disease: Additional follow-up results of a pilot study through 1 year. [2022]

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

Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. [2022]

3. Turkey pubmed.ncbi.nlm.nih.gov

The effects of transcutaneous auricular vagus nerve stimulation on visual memory performance and fatigue. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of transcutaneous vagus nerve stimulation on healthy cognitive and brain aging. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

"The Wandering Nerve Linking Heart and Mind" - The Complementary Role of Transcutaneous Vagus Nerve Stimulation in Modulating Neuro-Cardiovascular and Cognitive Performance. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

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

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Older Age and Longer Epilepsy Duration Do Not Predict Worse Seizure Reduction Outcome after Vagus Nerve Stimulation. [2018]

10. China pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. [2023]