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NIH grant 1IK2RD000580-01A2: Mechanisms of allostatic load in post-TBI brain aging: the relationship between autonomic flexibility and interoceptive neural networks
Institute: {'code': 'VA', 'abbreviation': 'VA', 'name': 'Veterans Affairs', 'admin_org_id': '12500964', 'admin_funding_url': ''}. PI: Abigail Waters. Award: $.
Start: 2026-10-01T00:00:00.
Significance to VA: Veterans remain at high risk for traumatic brain injury (TBI) in civilian life as they age, and
protracted recoveries from TBI appear to be influenced by factors outside of injury severity, such as chronic
stress. Interoceptive coding networks in the brain, which decline as individuals age, help to regulate chronic
stress through the autonomic nervous system (ANS), which can be disrupted after TBI. ANS dysfunction has in
turn been linked to increased cognitive impairment, reduced neuroplasticity, and attenuated benefit from
cognitive training interventions. Thus, older adults may be at higher risk for developing chronic neurobehavioral
deficits and reductions in brain health following TBI. The goal of this study is to characterize the relationship
between ANS function, allostatic load, interoception, and cognition in older Veterans with varying levels of
chronic TBI burden (geriatric vs. remote). Innovation and Impact: Preliminary data has shown that structural
connectivity of interoceptive networks in the brain in the acute period following traumatic brain injury (TBI) is
predictive of recovery over the next year, and furthermore, that memory, autonomic, and interoceptive
functions are associated in the subacute period following TBI in older adults. The proposed investigation
expands on my prior work by comparing cognitive functioning across different levels of chronic TBI burden (i.e.,
geriatric vs. remote), gaining understanding of allostatic load (characterized via blood-based biomarkers) on
ANS flexibility in response to cognitive load and interoceptive attention, through advanced statistical methods
for timeseries data. The proposed investigation will further my development as an independent investigator in
mechanisms and treatment development for Veterans at risk for AD/ADRD by refining my skills in ANS data
analysis, providing me with new skills in the use of fluid biomarkers in clinical research, and providing a
structured training plan in translational research and implementation science. Specific Aims: Specific Aim 1
will determine the relationship between ANS functioning and cognition, across Veterans with different levels of
chronic mmTBI burden. Specific Aim 2 will evaluate systemic and neural correlates of ANS dysfunction, to
identify prognostic biomarkers for post-TBI AD/ADRD cognition and targets for ANS-focused intervention.
Methodology: Over the course of the award period, we will enroll approximately 80 older Veterans (ages 65-
90) who have experienced a TBI, assessed via the OSU-TBI-ID Interview. Magnetic resonance imaging (MRI)
will be acquired for all participants and include structural and functional imaging (resting state and interoceptive
task developed by the applicant). Lab-based objective measurement of ANS flexibility (i.e., shapelet analysis of
heart rate variability) will be collected at rest, during a demanding cognitive task and during an interoceptive
task. Neurobehavioral assessment includes comprehensive neuropsychological testing, as well as blood-
biomarkers for allostatic load and AD/ADRD. Three Cohorts of Veterans will be recruited: (1) a “reference”
group consisting of Veterans with varying levels of adult Lifetime TBI burden, without a history of geriatric TBI
(N = 20), (2) a “Remote Geri” group of Veterans who also have varying levels of Lifetime TBI burden with the
additional burden of a Geriatric TBI, recruited outside of the “risk window” for developing post-TBI AD/ADRD at
5-7 years post-injury (N = 20), and (3) “at-risk” Veterans (N = 40) with three contributors to signs of accelerated
brain aging: varying levels of Lifetime TBI burden, burden associated with Geriatric TBI, and Proximity to
Geriatric TBI (i.e., 1-year post-geriatric TBI). Path to Translation/Implementation: Data generated from this
study will provide a mechanistic understanding of the allostatic-interoceptive system that may contribute to
post-TBI cognitive decline and risk for AD/ADRD, informing a larger, independent research program
developing (1) prognostic models informed by multi-modal neuroimaging markers of neuroplasticity and (2)
autonomic-focused, adjunctive interventions to improve response to cognitive rehabilitation.document fetched 2026-10-24 02:46