Trial Outcomes & Findings for Non-invasive Nerve Stimulation and Cognitive Training to Improve Cognitive Performance in Healthy Older Adults (NCT NCT04276805)

NCT ID: NCT04276805

Last Updated: 2026-07-27

Results Overview

The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. The total immediate recall score is the sum of correct words recalled after each of the 3 learning trials, which can range from 0 to 36.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

45 participants

Primary outcome timeframe

At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).

Results posted on

2026-07-27

Participant Flow

Participant milestones

Participant milestones
Measure
tVNS Group
Participants will undergo cognitive training paired with tVNS. Transcutaneous vagal nerve stimulation (tVNS): Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 2x sensory threshold (25Hz, 200 μs pulse width) using electrodes placed at the left tragus. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Sham Group
Participants will undergo cognitive training paired with sham stimulation. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Overall Study
STARTED
24
21
Overall Study
COMPLETED
24
21
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Non-invasive Nerve Stimulation and Cognitive Training to Improve Cognitive Performance in Healthy Older Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
tVNS Group
n=24 Participants
Participants will undergo cognitive training with tVNS Transcutaneous vagal nerve stimulation (tVNS): a non-invasive and safe technique that transiently enhances brain GABA and noradrenaline levels. cognitive training: A program of regular mental activities purported to maintain or improve one's cognitive abilities.
Sham Group
n=21 Participants
Participants will undergo cognitive training with earlobe sham cognitive training: A program of regular mental activities purported to maintain or improve one's cognitive abilities.
Total
n=45 Participants
Total of all reporting groups
Age, Continuous
73.13 years
STANDARD_DEVIATION 6.89 • n=9 Participants
73.29 years
STANDARD_DEVIATION 5.54 • n=27 Participants
73.20 years
STANDARD_DEVIATION 6.23 • n=267 Participants
Sex: Female, Male
Female
15 Participants
n=9 Participants
11 Participants
n=27 Participants
26 Participants
n=267 Participants
Sex: Female, Male
Male
9 Participants
n=9 Participants
10 Participants
n=27 Participants
19 Participants
n=267 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
4 Participants
n=9 Participants
2 Participants
n=27 Participants
6 Participants
n=267 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
20 Participants
n=9 Participants
19 Participants
n=27 Participants
39 Participants
n=267 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=9 Participants
0 Participants
n=27 Participants
0 Participants
n=267 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=9 Participants
0 Participants
n=27 Participants
0 Participants
n=267 Participants
Race (NIH/OMB)
Asian
1 Participants
n=9 Participants
2 Participants
n=27 Participants
3 Participants
n=267 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=9 Participants
0 Participants
n=27 Participants
0 Participants
n=267 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=9 Participants
1 Participants
n=27 Participants
2 Participants
n=267 Participants
Race (NIH/OMB)
White
21 Participants
n=9 Participants
18 Participants
n=27 Participants
39 Participants
n=267 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=9 Participants
0 Participants
n=27 Participants
1 Participants
n=267 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=9 Participants
0 Participants
n=27 Participants
0 Participants
n=267 Participants
Years of Education
16.83 years
STANDARD_DEVIATION 2.57 • n=9 Participants
16.43 years
STANDARD_DEVIATION 2.09 • n=27 Participants
16.64 years
STANDARD_DEVIATION 2.34 • n=267 Participants
Mini Mental State Examination (MMSE)
28.79 units on a scale
STANDARD_DEVIATION 1.32 • n=9 Participants
29.00 units on a scale
STANDARD_DEVIATION 1.00 • n=27 Participants
28.89 units on a scale
STANDARD_DEVIATION 1.17 • n=267 Participants

PRIMARY outcome

Timeframe: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).

The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. The total immediate recall score is the sum of correct words recalled after each of the 3 learning trials, which can range from 0 to 36.

Outcome measures

Outcome measures
Measure
tVNS Group
n=24 Participants
Participants will undergo cognitive training paired with tVNS. Transcutaneous vagal nerve stimulation (tVNS): Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 2x sensory threshold (25Hz, 200 μs pulse width) using electrodes placed at the left tragus. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Sham Group
n=21 Participants
Participants will undergo cognitive training paired with sham stimulation. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Hopkins Verbal Learning Test (Total Immediate Recall)
Baseline
26.50 units on a scale
Standard Deviation 3.99
24.86 units on a scale
Standard Deviation 4.95
Hopkins Verbal Learning Test (Total Immediate Recall)
Post-intervention
25.71 units on a scale
Standard Deviation 4.45
25.57 units on a scale
Standard Deviation 4.62

PRIMARY outcome

Timeframe: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).

The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. The total delayed recall score is the number of total correct words recalled (ranging from 0 to 12) after a 20-25 minute delay.

Outcome measures

Outcome measures
Measure
tVNS Group
n=24 Participants
Participants will undergo cognitive training paired with tVNS. Transcutaneous vagal nerve stimulation (tVNS): Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 2x sensory threshold (25Hz, 200 μs pulse width) using electrodes placed at the left tragus. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Sham Group
n=21 Participants
Participants will undergo cognitive training paired with sham stimulation. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Hopkins Verbal Learning Test (Total Delayed Recall)
Baseline
9.67 units on a scale
Standard Deviation 2.22
9.43 units on a scale
Standard Deviation 2.34
Hopkins Verbal Learning Test (Total Delayed Recall)
Post-intervention
9.04 units on a scale
Standard Deviation 2.07
9.10 units on a scale
Standard Deviation 2.74

PRIMARY outcome

Timeframe: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).

The Hopkins Verbal Learning Test-Revised (HVLT-R) is a verbal learning and memory measure involving learning a 12-item word list across three learning trials followed by delayed recall after approximately 20-25 minutes. The Total Retention score is calculated by dividing the delayed recall score (range: 0-12) by the higher score from Learning Trial 2 or Learning Trial 3 (range: 0-12) and multiplying by 100 to yield the percentage of words retained following the delay period. Higher percentage scores indicate better retention of learned information. A score of 100% indicates that delayed recall performance was equal to the participant's best learning trial. Percentage scores greater than 100% are possible when delayed recall performance exceeds the participant's highest score on Learning Trial 2 or Learning Trial 3.

Outcome measures

Outcome measures
Measure
tVNS Group
n=24 Participants
Participants will undergo cognitive training paired with tVNS. Transcutaneous vagal nerve stimulation (tVNS): Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 2x sensory threshold (25Hz, 200 μs pulse width) using electrodes placed at the left tragus. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Sham Group
n=21 Participants
Participants will undergo cognitive training paired with sham stimulation. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Hopkins Verbal Learning Test (Total Retention)
Baseline
91.43 percentage of words retained
Standard Deviation 19.38
93.34 percentage of words retained
Standard Deviation 17.24
Hopkins Verbal Learning Test (Total Retention)
Post-intervention
86.23 percentage of words retained
Standard Deviation 14.11
86.23 percentage of words retained
Standard Deviation 21.53

PRIMARY outcome

Timeframe: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).

The Hopkins Verbal Learning Test (HVLT-R) is a verbal learning and memory task with a 12-item word list learned over 3 trials. Within the delayed yes-no recognition part of the task, the participant is presented with a larger list or words and responds to whether each was on the original 12-item list. The recognition discrimination index score is calculated as number of hits (correctly identified words from the list) - number of false positive words (incorrectly identified words that were not on the list), with scores ranging from 0 to 12 (perfect score).

Outcome measures

Outcome measures
Measure
tVNS Group
n=24 Participants
Participants will undergo cognitive training paired with tVNS. Transcutaneous vagal nerve stimulation (tVNS): Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 2x sensory threshold (25Hz, 200 μs pulse width) using electrodes placed at the left tragus. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Sham Group
n=21 Participants
Participants will undergo cognitive training paired with sham stimulation. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Hopkins Verbal Learning Test (Recognition)
Baseline
10.71 units on a scale
Standard Deviation 1.27
9.86 units on a scale
Standard Deviation 2.74
Hopkins Verbal Learning Test (Recognition)
Post-intervention
10.29 units on a scale
Standard Deviation 1.27
10.29 units on a scale
Standard Deviation 2.12

PRIMARY outcome

Timeframe: At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling).

Population: One participant within the tVNS group was unable to complete NIH toolbox measures within the post-intervention assessment and was therefore excluded from pre-post intervention analyses.

The National Institutes of Health (NIH) Toolbox Fluid Cognition Composite is a standardized measure of fluid cognitive functioning derived from performance on five tests assessing attention, executive function, working memory, episodic memory, and processing speed (Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, Picture Sequence Memory, List Sorting Working Memory, and Pattern Comparison). Scores are reported as Fully Corrected T-scores derived from NIH Toolbox normative data and adjusted for demographic characteristics including age, sex, race/ethnicity, and education. Fully Corrected T-scores have a normative mean of 50 and standard deviation of 10. Higher T-scores indicate better fluid cognitive functioning, whereas lower T-scores indicate poorer fluid cognitive functioning. A T-score of 50 represents average performance relative to the normative population.

Outcome measures

Outcome measures
Measure
tVNS Group
n=23 Participants
Participants will undergo cognitive training paired with tVNS. Transcutaneous vagal nerve stimulation (tVNS): Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 2x sensory threshold (25Hz, 200 μs pulse width) using electrodes placed at the left tragus. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
Sham Group
n=21 Participants
Participants will undergo cognitive training paired with sham stimulation. Cognitive training: A structured program of mental exercises designed to maintain or improve cognitive abilities, completed for one hour daily over a two-week period using a web-based platform (Posit Science BrainHQ).
NIH Toolbox Fluid Cognitive Composite
Baseline
56.39 T-score
Standard Deviation 12.06
59.52 T-score
Standard Deviation 7.49
NIH Toolbox Fluid Cognitive Composite
Post-intervention
60.43 T-score
Standard Deviation 10.09
63.43 T-score
Standard Deviation 6.52

Adverse Events

tVNS Group

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Sham Group

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

John Williamson, PhD, ABPP-CN

University of Florida

Phone: 352-548-6920

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place