COVID-19 Delirium: Researchers From Trinity College Discover That Delirium in Most COVID-19 Patients Linked To Altered Glucose Metabolism in Brain
: Trinity College Researchers in Dublin have identified a connection between aberrant energy metabolism in the brain and delirium ie the state of impaired cognition in individuals who are unwell. This mental symptom is proving common in individuals hospitalized with COVID-19.
The research findings were published in the peer-reviewed Journal of Neuroscience
Although much of the research was conducted in mice, additional work suggests overlapping mechanisms are at play in humans because cerebrospinal fluid (CSF) collected from patients suffering from delirium also contained tell-tale markers of altered brain glucose metabolism.
The research also suggests that therapies focusing on brain energy metabolism may offer new routes to mitigating delirium.
Typically when the body experiences high levels of inflammation such as during bacterial or viral infections, our brain function changes, which in turn affect our mood and motivation. In older patients such acute inflammation can produce a profound disturbance of brain function known as delirium. Despite the disorder being relatively common, the mechanisms by which it arises are poorly understood.
The researchers found that artificially inducing peripheral inflammation in mice triggered sudden onset cognitive dysfunction, and that this is mediated by a disturbance to energy metabolism.
In study experiments, inflammation left the mice with lower levels of blood sugar (glucose), which the brain requires for maintaining normal function. When the animals were supplemented with glucose, their cognitive performance returned towards normal, despite the continued inflammation.
Dr Colm Cunningham, a Professor at the Trinity Biomedical Science Institute lab where the work was performed, said, "An important feature of these experiments was that mice with early stages of pre-existing neurodegenerative disease were far more susceptible to dysfunction when these metabolic changes occurred.
He further added, "Our collaborators in Oslo also detected evidence of altered brain glucose metabolism in cerebrospinal fluid taken from people experiencing delirium, which argues for overlapping mechanisms in humans and mice. In other words, the signs are that similar processes are at work in humans."
A critical care physician from Vanderbilt University, Dr Wes Ely, who wasn't involved with the study, commented, "The finding that the neurodegenerative animals are less resilient to this disturbance of energy metabolism really resonates with what we see in our intensive care unit patients with delirium."
Considering the frequency of delirium among hospitalized members of the elderly population and, given that these episodes can accelerate the progress of underlying dementia, treatments are desperately needed.
Dr Cunningham added, "Simply providing glucose to patients is not likely to treat delirium in most cases but collectively our data emphasize that an appropriate supply of both oxygen and glucose to the brain becomes especially important in older patients and in those with existing
dementia. Therefore, we believe that focusing on brain energy metabolism may offer routes to mitigating delirium."
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