# Investigating the Contribution of Peripheral versus Central Nervous System Immune Dysfunction to Cognitive Aging

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $175,934

## Abstract

Project Summary/Abstract
The insurgence of coronavirus disease 2019 (COVID-19) has disproportionately affected the older adult
population and raised numerous questions regarding long-term sequalae of the novel SARS-CoV-2 virus on
late life clinical outcomes. The pathological aging milieu is characterized by a ‘primed’ inflammatory state,
increased risk of Alzheimer’s disease-related protein deposition, and greater vulnerability to systemic
infections. We propose that the heterogeneity of clinical outcomes related to SARS-CoV-2 exposure may stem
from variability in the “host” immune milieu and the presence of AD-related pathology, which may interface to
negatively impact cognitive trajectories. As such, the overarching hypothesis of our administrative
supplement is that older adults who are exposed to SARS-CoV-2 virus will experience greater cognitive
decline, with worse outcomes noted in individuals with greater AD-related pathology and higher levels
of systemic inflammatory markers. The existing infrastructure of the parent R01 provides a critical platform
to appraise the effect of SARS-CoV-2 on aging outcomes, as our awarded grant funds the ascertainment of
biospecimens [blood; CSF], analyses of Alzheimer’s Disease-related pathology (i.e., Aß1-42; phosphorylated
tau; neurofilament light chain [NfL]) and analyses of inflammatory markers in 180 older adults over two time
points. In this administrative supplement, we propose to evaluate antibody levels (i.e., presence or absence) to
SARS-CoV-2 in serum at baseline and 2-year follow-up in the parent R01 cohort. SARS-CoV-2 exposure is
associated with both symptomatic and asymptomatic disease; to enrich the parent R01 cohort for the likelihood
of SARS-CoV-2 exposure, we will preferentially recruit 20 additional older adults with a history of confirmed
(i.e., RT-PCR test) COVID-19 disease. We will address the following Aims: to determine whether exposure to
SARS-CoV-2 exacerbates memory decline in community-dwelling older adults (Aim 1); and to elucidate
whether associations between SARS-CoV-2 exposure and memory outcomes are influenced by the presence
of Alzheimer’s Disease pathology and baseline immune status (Aim 2). We believe that the proposed study is
significant to the cognitive neuroscience of immune aging; by clarifying the role of virus exposure on cognitive
outcomes in late life, we will be poised to understand long-term neurological implications of SARS-CoV-2 on
cognition and Alzheimer’s disease pathology in community-dwelling older adults, which may ultimately guide
interventions for vulnerable populations.

## Key facts

- **NIH application ID:** 10190641
- **Project number:** 3R01AG058772-02S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Brianne Magouirk Bettcher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $175,934
- **Award type:** 3
- **Project period:** 2019-02-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190641

## Citation

> US National Institutes of Health, RePORTER application 10190641, Investigating the Contribution of Peripheral versus Central Nervous System Immune Dysfunction to Cognitive Aging (3R01AG058772-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190641. Licensed CC0.

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