Dealing with delirium caused by UTIs

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Cedars-Sinai researchers have found blocking the action of a protein called interleukin 6 (IL-6), part of the immune system, could help resolve the delirium that often accompanies a urinary tract infection (UTI) in older patients. Their study in laboratory mice could pave the way for clinical trials of IL-6 inhibitors as a treatment for UTI-associated delirium in humans.

Older women are among the most susceptible to developing UTIs, an infection of the bladder and urethra that causes urinary urgency and pain. UTIs can also cause delirium in older people, resulting in a sharp decline in mental abilities that triggers disoriented thinking.

“Up to one-third of older patients hospitalized with UTIs can experience some degree of confusion and reduced awareness of their surroundings,” said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and the study’s senior author.

“Delirium affects millions of patients a year in the U.S., contributing to longer hospital stays, long-term cognitive problems, and increased mortality,” he continued. “Delirium can be a tipping point from which patients never fully recover. This is well established. What is less well established is why this is happening.”

To better understand the specific biological mechanisms behind UTI-associated delirium, Lahiri and colleagues observed laboratory mice with and without UTIs in specially designed mazes. In an arena where the animals could move about freely, uninfected mice spent more time in the center of the chamber. Those with UTIs huddled in the periphery, suggesting they had higher levels of anxiety, a common symptom of delirium.

In a Y-shaped maze with three arms to explore, uninfected mice tended to explore all three arms, while mice with UTIs kept returning to the same arm, suggesting a lapse in short-term memory, another feature of delirium.

The investigators also observed structural changes in the brains of mice with UTIs. In a previous study led by Lahiri, investigators found a connection between ventilatorinduced lung injury and delirium. Lahiri and colleagues theorized in both cases this was because of the reaction of IL-6, which helps regulate immune response to the lung injury or the UTI.

“Occasionally, when the response of IL-6 is excessive, our research indicates there can be brain injury,” Lahiri said. “IL-6 induces changes within the neurons our studies connected with delirium-like behavior. This is the first time this type of structural and functional change has been demonstrated. We’ve now shown two distinct models of this connection, one non-infectious and one infectious.”

In the current study, when investigators treated some of the infected mice with antibodies that blocked the effects of IL-6, the delirium-like behavior of those animals was resolved.

“Treatment with anti-IL-6 antibody in the UTI group normalized all the brain changes, both structural and functional,” Lahiri said. “A wealth of studies have shown a link between IL-6 and delirium, but only this study and our previous study have shown IL-6 may play a direct pathological role in delirium.”

If symptoms are treated early, he added, full recovery is possible. The next step is to design clinical trials with anti-IL-6 antibodies as a treatment for patients with UTIinduced delirium.

Lahiri believes the model he and coinvestigators created could be used to study delirium in other conditions associated with increased incidence of UTI. These include those with pre-existing neurologic disorders like Alzheimer’s disease, Parkinson’s disease, stroke, and multiple sclerosis where delirium can be hard to distinguish from the underlying disease but is important to treat.

“A huge population stands to benefit from these investigations” he said. “We’re looking to apply this model to these other systemic disease conditions and states where the brain dysfunction caused is potentially reversible.” (Cedars-Sinai provided this information.)

“Delirium can be a tipping point from which patients never fully recover. This is well established. What is less well established is why this is happening.”

Study: Many baby boomers without dental insurance

Arecent survey by Value Penguin found almost 40% of baby boomers are unlikely to have dental insurance coverage, in part, due to Medicare.

Key findings of the survey include: • Baby boomers are the least likely to have dental insurance, and most say it’s due to Medicare. Of the survey respondents, 38% of baby boomers don’t have dental insurance, and 42% within that group say it’s because their Medicare plan doesn’t cover dental coverage. • Nearly 30% of those without dental insurance regret not being covered. And 30% of all Americans (both insured and uninsured) regret not taking better care of their teeth. • Nearly half (48%) of Americans with dental insurance have skipped dental visits or recommended procedures due to the cost. Among those who aren’t insured, 65% have skipped the dentist for the same reason. • Those without dental insurance are twice as likely to be unhappy with their teeth as those who are insured. More than one-third (34%) of those without insurance aren’t satisfied with the condition of their teeth, compared with 17% of those who are insured. • As for consumers who have dental insurance, their main gripe is not enough services or procedures are covered (cited by 25%). In total, 48% of insured Americans have at least one complaint about their dental insurance policy or insurer. (Value Penguin provided this information.)