# Nosocomial pneumonias impair cognitive function

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 2023 · $464,129

## Abstract

PROJECT SUMMARY/ABSTRACT
Patients in intensive care units are at high risk for long-term health threats including cognitive impairment. The
correlation was only recently revealed after large-scale follow-up cognitive assessments on intensive patient
survivors after their discharge from the hospital. There are testimonials, reviews and calls-to-action on many
critical care websites and in journal issues over the last decade on this public health crisis. Studies have
implicated delirium as a good predictor for long-term cognitive deficit; however, the causative and molecular
mechanisms leading to abrupt cognitive impairment are unclear.
In the past 4 years, our studies have discovered that patients in the intensive care unit who contracted
bacterial pneumonia have elevated levels of cytotoxic amyloids in the bronchoalveolar lavage fluid, plasma,
and the cerebrospinal fluid. Rodent brain slices incubated in the cerebrospinal fluids collected from bacterial
pneumonia-positive patients show dampened hippocampal long-term potentiation. In comparison, synaptic
strengthening is prominent in slices incubated in bacterial pneumonia-negative patients’ cerebrospinal fluid.
Moreover, immunopurified from the cerebrospinal fluid or plasma using selective antibodies against Aβ and 𝜏
oligomers and injected into rodents, these cytotoxins induce neuronal dendritic spine retraction, reduce spine
density, and impair animal learning.
Our previous in vitro studies have implicated that in response to Pseudomonas aeruginosa infection, lung
endothelium produces and releases cytotoxins including Aβ and 𝜏 species, and the cytotoxicity and bioactivity
of these species are dependent upon the bacterial virulence. These endothelium-derived cytotoxins damage
endothelial barrier integrity, hinder vascular repair following injury and, importantly, they are released into the
systemic circulation in vivo. Thus, in this competitive renewal, the studies are designed to test the hypothesis
that bacterial pneumonia-elicited lung endothelium-derived amyloids include pathological Aβ and 𝜏 species
capable of dissemination and initiating aggregation. This work addresses a novel mechanism underlying the
end organ dysfunction by systemically quantify cytotoxins released from endothelium in vitro, in rodents, and in
patient specimens.

## Key facts

- **NIH application ID:** 10623293
- **Project number:** 5R01HL140182-06
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** Mike Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $464,129
- **Award type:** 5
- **Project period:** 2018-04-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10623293

## Citation

> US National Institutes of Health, RePORTER application 10623293, Nosocomial pneumonias impair cognitive function (5R01HL140182-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10623293. Licensed CC0.

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