Alzheimer Disease, Aging
Conditions
Brief summary
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.
Interventions
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).
Sponsors
National Institute on Aging (NIA)
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Masking description
Because the active electrode will be placed on the cymba conchae and the sham on the earlobe, full double-blinding is not feasible; as such, the experimenter will be aware of the active/sham condition status of each experimental block. Participants will be masked/blinded to condition order and hypotheses (they will not be informed which blocks are active vs. sham).
Intervention model description
The study will use a sham-controlled, single-blind, within-subject, counterbalanced, randomized design. Each participant will complete four blocks (two active and two sham stimulation) in a counterbalanced within-subject design using an ABBA or BAAB order (A = active taVNS, B = sham stimulation). To ensure equal numbers per order, order will be deterministically assigned by subject ID parity: odd = ABBA, even = BAAB. Subject IDs will be issued sequentially within the age group, yielding balance in both Young and Older groups and effective random assignment of participants to order condition.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Recognition Memory (d-prime) | post-active vs post-sham stimulation; up to 2 hours of task | 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). |
Countries
United States
Outcome results
None listed