The Locus Coeruleus, Norepinephrine and Cognitive Aging

NCT06880510 | Active Not Recruiting FDA Device

• 1 other identifier: 1910009087
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (5)

• Tonic pupil size in mm

  The investigators will continuously monitor tonic pupillary size to determine whether it is affected by taVNS. To do so, the investigators will use a EyeLink 1000+ eyetracker and measure pupil diameter continuously throughout the completion of computer-based cognitive tasks, such as an Oddball task, Attentional Boost Effect task, Proactive Interference task, or Tone Gap task. Tonic pupil size are measured with custom software, and pupil size is reported in mm.

  15-45 minutes

• Heart rate variability

  The investigators will continuously monitor heart rate using photoplethysmography (BIOPAC Systems) to calculate heart rate variability, to determine whether it is affected by taVNS. Root mean square of successive differences (RMSSD) will be the specific heart rate metric used.

  15-45 minutes

• Discriminability index on tests including the attentional boost effect task

  The investigators will test performance on measures of attention (e.g. Oddball paradigm, Flanker inhibitory control paradigm, attentional boost effect paradigm) to determine whether performance on this task, specifically d' (discriminability index) is affected by taVNS.

  15-45 minutes

• Phasic pupillary responses in mm

  The investigators will monitor phasic pupillary response size to determine whether they are affected by taVNS. To do so, the investigators will use a EyeLink 1000+ eyetracker and measure pupil diameter continuously throughout the completion of computer-based cognitive tasks, such as an Oddball task, Attentional Boost Effect task, Proactive Interference task, or Tone Gap task. Phasic pupil sizes are measured with custom software, and response size is reported in mm.

  15-45 minutes

• Reaction time on tests including the attentional boost effect task

  The investigators will test performance on measures of attention (e.g. Oddball paradigm, Flanker inhibitory control paradigm, attentional boost effect paradigm) to determine whether performance on this task, specifically reaction time, is affected by taVNS.

  15-45 minutes

Study Arms (1)

Cornell University

EXPERIMENTAL

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.

Device: t-VNS transcutaneous auricular vagus nerve stimulator

Interventions

t-VNS transcutaneous auricular vagus nerve stimulator DEVICE

An investigator will clip the the transcutaneous auricular vagus nerve stimulator (taVNS) to the outer ear, and apply electrical current to modulate the activity of the vagus nerve. During this process, the investigator will monitor pupil size and heart rate to determine whether either of these variables is affected by vagus nerve stimulation.

Cornell University

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• + years of age
• Able to speak and understand English
• Hearing and vision correctable to normal or near-normal
• Willing and able to use a touchscreen
• Willing and able to use a keyboard and mouse
• Willing and able to undergo a MRI scan at the Cornell MRI Facility lasting approximately 90 minutes.

You may not qualify if:

• Moderate or severe brain injury
• Serious neurological disorders such as epilepsy
• Recent concussion
• Colorblindness
• Use of street drugs
• Cardiac arrhythmias

Sponsors & Collaborators

• Cornell University: lead

Study Sites (1)

Cornell University

Ithaca, New York, 14850, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2024
• First Posted: March 17, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Indefinitely.
• Access Criteria: The data may be posted on Open Science Framework if required by publications.

Locations

US (1)