# Microglia mediate cognitive dysfunction in elderly survivors of pneumonia

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2022 · $440,000

## Abstract

PROJECT SUMMARY
Multiple lines of clinical evidence demonstrate a link between pneumonia, cognitive impairment, and dementia
in the elderly. The mechanisms underlying this susceptibility, however, remain unclear. Clinical and experimental
evidence suggests that microglia – resident macrophages in the brain – play a key role in both maintaining
normal brain homeostasis and upon activation can drive neurodegeneration and cognitive decline. The role of
microglia in cognitive decline in elderly survivors of pneumonia is unknown. In this R21, we propose to test two
high-risk, high-reward hypotheses: First, we hypothesize that cell-autonomous changes in microglia with
aging necessary for the persistent cognitive decline after pneumonia in old animals. Second, we
hypothesize that transcriptomic changes in the microglia and brain observed in mice after pneumonia will
mirror those observed in patients with pneumonia. We propose to test these hypotheses with two Specific
Aims. Aim 1. To determine whether cell-autonomous, age-related dysfunction in microglia precludes
cognitive recovery in old mice following influenza A virus-induced pneumonia. We will use
pharmacological approaches to deplete microglia in young and old mice during recovery from influenza A
infection and measure performance on cognitive tests, and transcriptomic changes in microglia and the brain
using RNA-Seq with validation using spatial transcriptomics. Aim 2. To compare microglial activation in
patients who succumb to SARS-CoV-2 pneumonia with other pneumonia and non-pneumonia controls.
We will collect hippocampal tissue during a rapid autopsy in patients who die after SARS-CoV-2 pneumonia and
analyze it using single-cell RNA-seq and spatial transcriptomics.

## Key facts

- **NIH application ID:** 10354214
- **Project number:** 1R21AG075423-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** GR Scott Budinger
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $440,000
- **Award type:** 1
- **Project period:** 2022-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354214

## Citation

> US National Institutes of Health, RePORTER application 10354214, Microglia mediate cognitive dysfunction in elderly survivors of pneumonia (1R21AG075423-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10354214. Licensed CC0.

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