Aging
Conditions
Brief summary
Decline in brain health and associated loss of cognitive function in healthy aging decreases quality of life.We need better tools to both enhance brain health and improve cognitive performance in healthy brain aging so that it can be delayed, reduced, or even reversed. The present proposal is designed to evaluate the pairing of cognitive training with a non-invasive neurostimulation technology that has shown promise in both increasing neuroplasticity and in enhancing cognitive performance, transcutaneous vagal nerve stimulation (tVNS).
Detailed description
Decline in brain health and associated loss of cognitive function in healthy aging decreases quality of life. We need better tools to both enhance brain health and improve cognitive performance in healthy brain aging so that it can be delayed, reduced, or even reversed. Auricular or transcutaneous vagal nerve stimulation (tVNS) is a low cost, easy to use, safe, and non-invasive approach for potentially enhancing brain systems important for cognition, neuroplasticity, and brain health. The afferent path of the vagus travels through the nucleus of the solitary tract and the locus coeruleus, which both project to the hippocampus, a structure important in encoding new memories. The locus coeruleus is also the brain's primary source of norepinephrine. As the brain ages, there is a significant decline in the number and health of neurons, including in the pathway of the locus coeruleus. The release of norepinephrine in the medial temporal regions including the hippocampus, and the frontal lobes may enhance synaptic plasticity in critical cognitive areas and VNS upregulates norepinephrine. The present proposal is designed to evaluate the pairing of cognitive training with transcutaneous vagal nerve stimulation (tVNS). The investigators have a collaborative relationship with the phase III Augmenting Cognitive Training (ACT) study team, which pairs a different non-invasive approach to brain stimulation (tDCS) with cognitive training. The investigators will leverage the existing ACT infrastructure developed through the support of NIA and the MBRF to evaluate tVNS and a cognitive training program in a two-week intervention with before and after cognition and multi-modal MRI assessments to determine brain function, plasticity, and cognitive modifications resulting from the intervention.
Interventions
The active tVNS group will receive 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. The sham group will receive sham stimulation (0x sensory threshold) using electrodes placed on the left earlobe.
BEHAVIORALCognitive training
Cognitive training will be delivered for one hour daily over a two-week period via a web-based program (Posit Science BrainHQ, accessed through www.positscience.com) containing eight adaptive tasks targeting attention, processing speed, and working memory. Participants will complete four randomly selected tasks per hour of training.
Sponsors
University of Florida
University of Arizona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy individuals willing to commit to study requirements
Exclusion criteria
* Neurological disorders to include traumatic brain injury. * Evidence of dementia . * Major psychiatric illness * Unstable and chronic medical conditions. * MRI contraindications (e.g., pregnancy, claustrophobia, metal implants that are contraindicated for MRI). * Physical impairment precluding motor response or lying still or walking * Hearing or vision deficits that will not allow for completion of assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hopkins Verbal Learning Test (Total Immediate Recall) | 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. |
| Hopkins Verbal Learning Test (Total Delayed Recall) | 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. |
| Hopkins Verbal Learning Test (Total Retention) | 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. |
| Hopkins Verbal Learning Test (Recognition) | 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). |
| NIH Toolbox Fluid Cognitive Composite | 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 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJohn Williamson, PhD
University of Florida
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 73.20 years STANDARD_DEVIATION 6.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mini Mental State Examination (MMSE) | 28.89 units on a scale STANDARD_DEVIATION 1.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 39 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 9 Participants |
| Years of Education | 16.64 years STANDARD_DEVIATION 2.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 21 |
| other Total, other adverse events | 0 / 24 | 0 / 21 |
| serious Total, serious adverse events | 0 / 24 | 0 / 21 |
Outcome results
None listed