Patients at the ICU often show dementia-like symptoms.
Recently, a lot of attention in the scientific community has been focused on patients in the Intensive Care Unit (ICU) who go on to develop cognitive deficits. Cognitive deficit or impairment is a general term that can cover many symptoms, such as memory loss or impairment, difficulty paying attention or focusing, and trouble with organizing or planning. These symptoms are very similar to Alzheimer’s and other forms of dementia.
It is estimated that one fourth to two thirds of patients who have had a critical illness will go on to develop cognitive deficits. Some patients will fully recover over time, and some will not. The question that doctors and researchers are asking is what causes these deficits in ICU patients?
I spoke with Dr. Troy Stevens, the director of the Center for Lung Biology at the University of South Alabama, about the work from his lab on the link between the lung, ICU stays, and cognitive deficits.
Maybe you’re wondering (because I was) how someone who studies lungs gets interested in what is basically a brain problem. That’s because Stevens’ lab studies a type of bacteria called Pseudomonas aeruginosa, which causes pneumonia. More than half of ICU patients will be placed on a mechanical ventilator and patients on ventilators are more likely to develop ventilator-associated pneumonia.
Tau in the lungs
Pseudomonas aeruginosa has a type 3 secretion system, which is the bacterial version of a syringe. This secretion system injects bacterial enzymes into the host cell. Previous research by Stevens’ lab has shown that one of these enzymes, named ExoY, increases endothelial cell permeability. (Endothelial cells line the inside of blood vessels, and normally form a very tight barrier. Increased endothelial permeability can lead to leaky vessels, which in the lung can cause fluid to accumulate in the airspace). ExoY increases permeability by destabilizing microtubules (these act as the scaffold of the cell, like the frame of a building).
Ongoing work in the lab indicates that the microtubules become destabilized when a microtubule binding protein called tau is altered. Tau becomes insoluble and aggregated and is secreted by the cell. In non-science terms, this altered form of tau becomes sticky and lumpy and the cell spits it out. Dr. Stevens’ group has found insoluble and aggregated tau in the blood and lung fluid of animals infected with Pseudomonas. This disease model embodies what he calls ‘an infectious tauopathy of the lung’.
Tau in the brain
Interestingly, Alzheimer’s and other neurodegenerative diseases (also called tauopathies) are associated with the aggregation of tau in the brain. Currently, it’s not known whether ICU patients with cognitive deficits have aggregated tau in their brains which is responsible for their altered mental status. It’s also unknown whether ICU patients with lung problems follow the animal model of Pseudomonas infection by shedding tau into the blood and lungs.
Planned future studies will determine if tau is present in the lungs and blood of ICU patients with pulmonary problems, and if they are more likely to have cognitive impairment than patients in the ICU for other reasons. A long-term follow-up study of ICU patients is needed to determine whether lung tauopathies lead to brain tauopathies, and whether patients with lung tauopathies are more likely to develop dementia.
For more information on ICU patients and cognitive deficits, you can check out several articles:
Pandharipande PP1, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. (2014). Long-Term Cognitive Impairment after Critical Illness New England Journal of Medicine, 370 (2), 184-186 DOI: 10.1056/NEJMc1313886
Bohannon, R., Maljanian, R., & Ferullo, J. (2013). Mortality and readmission of the elderly one year after hospitalization for pneumonia Aging Clinical and Experimental Research, 16 (1), 22-25 DOI: 10.1007/BF03324527
icu, cognitive deficit, lung, intensive care, alzheimers, tau