UTIs and other types of infections are closely associated with delirium, a short-term confusional state. About 30 percent of older people with UTIs develop delirium, and infections account for about half of delirium cases.
“I’m not sure patients, the general public knows how UTIs can do this,” said Shouri Lahiri, associate professor of neurology, biomedical sciences and neurosurgery at Cedars-Sinai Medical Center. “If they’re having confusion episodes, it’s an opportunity to seek out medical advice, to evaluate for an underlying UTI. And in doing so, not only will you preserve short-term cognition, but perhaps even long-term cognitive function.”
How delirium can contribute to dementia
Delirium is an acute confusional state of mind, and its hallmark characteristics — inattention, executive dysfunction and short-term memory impairment — fluctuate in severity. Triggers for delirium include infections as well as certain medical procedures and medication.
Delirium is typically thought of as a temporary cognitive state, but if its cause remains “unresolved or untreated, the delirium can accelerate, can become more and more severe,” Lahiri said. “It can leave a mark that’s permanent.”
It is also surprisingly common, especially among hospitalized patients. Some studies estimate that 15 to 30 percent of patients in hospital wards and up to 70 percent of patients who are critically ill develop delirium. Annually, more than 2.6 million Americans older than 65 years develop delirium.
Some people incorrectly think that delirium is normal for an old person.
“People think delirium is safe,” said Wes Ely, professor of medicine and co-director of the Center for Critical Illness, Brain Dysfunction, and Survivorship at Vanderbilt University Medical Center. “It’s very, very dangerous. It’s a pretty absolutely precarious thing for somebody to go into delirium.”
In the short term, “delirium increases hospital length of stay, it is associated with increased mortality,” Lahiri said. “It’s associated with unimaginable human suffering.”
Older adults are more susceptible to delirium because they probably have age-related changes to their blood-brain barrier and less “brain reserve” to compensate for additional challenges to their brain.
But delirium also has costs in the long term if not properly managed.
“It’s something that accelerates chronic brain dysfunction,” Lahiri said. “I think of it as being a modifiable risk factor for Alzheimer’s disease and related dementias, because by mitigating it, you can reduce progression of these diseases.”
Research has shown that people who were diagnosed with dementia and then developed delirium had double the rate of cognitive decline when compared to those who didn’t. There is also a dose-response effect of delirium on long-term cognition: the more severe the delirium, the higher the risk of dementia.
Infections increase risk of dementia
There is emerging evidence that infections, including UTIs, are themselves associated with an increased risk for dementia. A 2021 study tracked the electronic health records of 989,800 adults age 65 and older with no previous history of dementia or cognitive impairment in the United Kingdom.
After controlling for a wide range of other factors such as sex, ethnicity, smoking and alcohol consumption, researchers found that, overall, people who had any infection had 1.53 times the risk of developing dementia compared with people without infection.
The more severe the infection, such as with sepsis and pneumonia, the higher the likelihood of subsequently developing dementia. People who were hospitalized had it worst, with nearly double the risk for dementia. But even milder infections, including UTIs, heightened the risk of subsequent dementia by 1.73 times.
The study was associational, so it cannot prove causation. People with dementia are also more likely to develop infections, for example. But the risk remained elevated even up to nine or more years after infection.
“What’s really needed now is to really understand the mechanisms behind this association between infections and dementia,” said Rutendo Muzambi, a research fellow at the London School of Hygiene & Tropical Medicine and an author of the study. Clinical trials that examine whether strategies to reduce infections lower the risk of dementia are also needed, she said.
One common factor may be inflammation caused by an immune response to the infection — first of the body, which can then spread to the brain.
The brain’s frontal lobes, which are important for executive function, and the hippocampus, which is crucial for memory, are particularly affected in delirium, said Ely, who was a co-author of a review about delirium in 2020.
In a 2021 study, Lahiri and his colleagues reported that mice with UTIs behaved in a delirium-like way — they were more anxious in mazes compared with mice that did not have a UTI. These behavioral changes correlated with increased inflammatory cytokines and neuronal changes in the mice’s frontal cortexes and hippocampuses.
“Those cells are injured, and they’re not behaving well, which is why the patient can get confused,” Ely said. “And if that process continues to go on and those cells die, that’s when you have the acquisition of dementia.”
How to reduce the risk for UTIs, delirium and dementia
Keep hydrated and urinate often to reduce the risk of UTIs. Notice if urination becomes painful, difficult or frequent, or you start having fever, chills or fatigue.
Promptly seek medical treatment when experiencing UTIs. This will reduce the risk of known serious complications, including delirium and sepsis, though more evidence is required for whether this would also prevent dementia risk, Muzambi said.
For caregivers, keep loved ones with delirium reoriented. Keep them mobilized, and make sure they get good sleep at night and are awake during the day, said Ely, author of “Every Deep-Drawn Breath,” a book about critical care and delirium.
Do you have a question about human behavior or neuroscience? Email BrainMatters@washpost.com and we may answer it in a future column.