# Establishing Mechanisms Between Traumatic Brain Injury and Dementia Using Epidemiology, Clinical Studies, Blood-Based Biomarkers, and Neuroimaging Biomarkers

> **NIH NIH K23** · UNIVERSITY OF PENNSYLVANIA · 2024 · $229,270

## Abstract

PROJECT SUMMARY / ABSTRACT
Traumatic brain injury (TBI) is common and is associated with significant morbidity and mortality. The sequelae
from TBI can be long-lasting, and multiple studies have reported an increased rate of cognitive decline and higher
risk of dementia among persons with TBI. However, the mechanisms linking TBI to dementia remain poorly
understood, although vascular dysfunction, neuroinflammation, and aggregation of proteins have been
proposed. This gap in knowledge was recently highlighted in the 2020 Lancet Commission on Dementia, which
added TBI as one of twelve potentially modifiable risk factors for dementia, and in the 2019 NINDS Alzheimer’s
Disease-Related Dementias (ADRD) Summit, which formally recommended further study into the role of TBI in
dementia, including an emphasis on studying mechanism and developing TBI-AD/ADRD-related biomarkers. To
directly address this research need, this application builds on my prior NINDS R25 award and proposes to use
epidemiology, clinical studies, and vascular-related blood-based and neuroimaging biomarkers to investigate
vascular injury and subsequent vascular dysfunction as mechanisms linking TBI and dementia.
The central hypothesis of this proposal is that TBI is associated with cognitive decline and dementia risk in part
via vasculopathy-mediated pathways which accelerate neurodegeneration for years post-TBI. This proposal will
leverage existing data from 2 ongoing prospective cohort studies (Aims 1 and 2) and new data from a
prospectively recruited cohort (Aim 3). The aims of this study are: 1) to determine if acute vascular injury is
associated with poor short-term TBI-related cognitive outcomes in the trauma center-based Transforming
Research and Clinical Knowledge in TBI (TRACK-TBI) Study, 2) to investigate if chronic vascular dysfunction
mediates associations of TBI with poor long-term cognitive outcomes in the community-based Atherosclerosis
Risk in Communities (ARIC) Study, and 3) to evaluate if the trajectory of post-TBI vascular dysfunction is
associated with short-term cognitive outcomes in a prospectively recruited cohort nested within ongoing studies
at the University of Pennsylvania Trauma Center. The overall objective of this proposal is to use multi-modal
biomarkers of vasculopathy to investigate mechanisms linking TBI and neurocognitive outcomes and to identify
time-periods during which future interventions may be effective at preventing TBI-related dementia.
In addition to the proposed research, this project will provide me with critical gap-based training, including in the
design, conduct, and implementation of clinical-epidemiologic studies and in the use of biomarkers as a method
to investigate disease mechanisms linking TBI to outcomes in clinical-epidemiologic studies. This training will
enable me to build an independent research program focused on vascular health in TBI with the goal of
elucidating disease mechanisms and characterizing TBI outcomes using wel...

## Key facts

- **NIH application ID:** 10833704
- **Project number:** 5K23NS123340-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Andrea Lauren Christman Schneider
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $229,270
- **Award type:** 5
- **Project period:** 2022-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833704

## Citation

> US National Institutes of Health, RePORTER application 10833704, Establishing Mechanisms Between Traumatic Brain Injury and Dementia Using Epidemiology, Clinical Studies, Blood-Based Biomarkers, and Neuroimaging Biomarkers (5K23NS123340-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10833704. Licensed CC0.

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