NIH grant: Contribution of Allostatic Load and Interoception to Brain Aging and Risk for AD/ADRD (1K23AG093089-01A1)

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NIH grant 1K23AG093089-01A1: Contribution of Allostatic Load and Interoception to Brain Aging and Risk for AD/ADRD
Institute: {'code': 'AG', 'abbreviation': 'NIA', 'name': 'National Institute on Aging', 'admin_org_id': '12500002', 'admin_funding_url': ''}. PI: Abigail  Waters. Award: $191832.
Start: 2026-08-15T00:00:00.
The objective of this K23 proposal is to foster my development as an independent investigator toward a clinical
science career in brain aging research. Specifically, my research interests are in predicting cognitive
trajectories in older adults by examining neural compensatory mechanisms (e.g., neuroplasticity, immune-
stress responses), and in developing interventions which address these mechanisms, using them to reduce
risk for Alzheimer’s disease (AD) and AD-related dementias (ADRD). As a neuropsychologist, I have gained
clinical experience in the assessment of neurodegenerative diseases, as well as research experience with
using multimodal neuroimaging to examine cognitive and neurophysiological mechanisms in brain aging. To
ensure an independent career in translational research, the proposed training plan will address (1) the
development of expertise in clinical research with complex, multi-modality data, training in timeseries analyses
and fluid biomarkers, and (2) mentorship to transition to a translational research career with independence in
all aspects of research development and management
The goal of the proposed study is to characterize the relationship between cognition and multiple levels of the
autonomic regulatory system, including the neural functioning of predictive coding networks, autonomic
flexibility in response to cognitive load, and multi-system stress burden biomarkers. Preliminary data from my
post-doctoral work in older adults recovering from mild traumatic brain injury, show strong associations
between memory, autonomic functions, and predictive coding networks. This study will expand on my prior
work by examining these relationships in older adults at varying risk for AD/ADRD, gaining understanding of
autonomic burden impact through use of blood-based biomarkers, and advanced statistical methods to
characterize ANS flexibility in response to cognitive load. Over the course of the award period, we will enroll
approximately 75 older adults (ages 65-90), with a stratified recruitment strategy across cognitive phenotypes
from normal aging to mild cognitive impairment (amnestic and non-amnestic). Magnetic resonance imaging will
be acquired for all participants and include structural, metabolic, and functional imaging (resting state and
interoceptive fMRI task developed by the applicant). Lab-based objective measurement of autonomic flexibility
will be collected at rest, during cognitive assessment. Neurobehavioral assessment includes comprehensive
neuropsychological testing, as well as multi-system stress burden biomarkers and AD/ADRD. Specific Aim 1
will determine the relationship between cognition, autonomic flexibility, and different levels of the autonomic
regulatory system. Specific Aim 2 will measure the moderating impact of cognitive phenotype on these
relationships, to generate effect sizes for future proposals. Data generated from this study will have direct
relevance to prognostic models of brain aging and interventions aimed at reducing risk for AD/ADRD,
launching an independent line of research.

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