Vagus Nerve Stimulation to Enhance Memory in Aging (VNS)

The aim of this study is to determine whether non-invasive vagus nerve stimulation enhances memory formation in cognitively healthy older adults and whether the effects of stimulation depend on gut and brain health.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer Disease; Aging
• Intervention / Treatment: Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Ages 18-30 years or 65-80 years
• Normal or corrected-to-normal vision (visual acuity)
• Fluent in English

Exclusion Criteria:

• Pregnant
• Symptoms of memory loss
• History of a neurological, psychiatric, or medical condition that could affect cognition or preclude MRI or pupillometry
• Use of medications known to alter cognition
• For older adults, neuropsychological performance that falls outside 1.5 standard deviations of age-adjusted norms and no self-reported memory or attention complaints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active vagus nerve stimulation; Participants will receive active stimulation during memory encoding of picture-word pairs. Active stimulation will occur during two learning phases of the learning and memory task. The total duration of these two phases will be less than 30 minutes.	Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); Non-invasive vagus nerve stimulation will be delivered with a well-validated device. taVNS delivers stimulation on the left ear, with the placement of the stimulating electrode differing between the active and sham conditions. Stimulation will occur during each learning trial (total of 30 trials per phase).
Sham Comparator: Sham stimulation; Participants will receive sham stimulation during memory encoding of picture-word pairs. Sham stimulation will occur during two learning phases of the learning and memory task. The total duration of these two phases will be less than 30 minutes.	Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); Non-invasive vagus nerve stimulation will be delivered with a well-validated device. taVNS delivers stimulation on the left ear, with the placement of the stimulating electrode differing between the active and sham conditions. Stimulation will occur during each learning trial (total of 30 trials per phase).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Recognition Memory (d-prime)	d' is a signal-detection sensitivity index-how well participants discriminate old (studied) from new (unstudied) items, independent of response bias. Computed as d' = Z(hit rate) - Z(false-alarm rate) from the old/new recognition memory test. Primary analysis is within-person Δhigh-confidence d' (based on "sure old" responses in the 4-point "sure old", "unsure old", "unsure new", "sure new" scale, Δ = active - sham) and Δoverall d' (based on "sure old" and "unsure old" responses). Main comparison is older vs. young, and within the older group also testing moderation by gut-brain axis measures and interactions with preclinical Alzheimer's disease pathology (pTau217, pTau181, Aβ42:40).	post-active vs post-sham stimulation; up to 2 hours of task

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Anthony D Wagner, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: October 2, 2025
• First Submitted That Met QC Criteria: October 2, 2025
• First Posted (Estimated): October 9, 2025

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: VNS102025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All other data will be made available via Stanford's Digital Repository (SDR) and will be linked with associated analytic code on the Stanford Memory Lab's Github. Additionally, the task and analysis scripts, along with comments explaining the source code and instructions to install and configure software required to run the scripts, will be shared via the website of the Stanford Memory Lab and our repository on GitHub. SDR is accessible to investigators who are not affiliated with Stanford University and does not require data to be associated with a publication prior to being accepted by the repository. This data archiving approach ensures that the broader scientific community will have long-term access to all data and analysis code.
• IPD Sharing Time Frame: The data will be made available upon publication of corresponding results or at the end of the award period, whichever is sooner. They will remain available indefinitely or until the end-of-life of the corresponding data-hosting platforms, if no suitable alternative can be identified.

IPD Sharing Access Criteria

De-identified MRI and other components of the dataset will be findable and identifiable via persistent Stanford Digital Repository (SDR) URLs. These links will be embedded in published preprints and manuscripts, as well as with direct links on the Stanford Memory Lab's webpage. The SDR does not require data to be associated with a publication to be accepted by the repository. Processed microbiome data tables and metadata will be findable and identifiable through GEO accession numbers. The raw sequencing data will be findable and identifiable through SRA accession numbers.

Access to de-identified data will not be controlled (i.e., once publicly available, anyone can access the de-identified data).

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No