How Urinary Tract Infections Trigger Delirium in People With Dementia

Urinary tract infections (UTIs) are among the most common infections in older adults, but in people living with dementia, they can trigger a sudden and dramatic change in behavior and cognition. A UTI that might cause mild discomfort in a younger, healthier person can instead set off delirium — an acute, fluctuating state of confusion — in someone with Alzheimer’s or a related dementia.

Dr. Shouri Lahiri is director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and leads the Lahiri Lab. His research focuses on the inflammatory mechanisms that link acute illnesses and infections to delirium and cognitive decline, including the role of immune signaling in brain changes during infection.

In this conversation with Being Patient founder Deborah Kan, Lahiri explained why up to one-third of older adults with a UTI can develop delirium, and why that risk is even higher for people with dementia, who have less cognitive reserve to draw on. He discussed why early antibiotic treatment is critical and what caregivers can do — from monitoring hydration and sleep-wake cycles to recognizing subtle signs of urinary discomfort — to help prevent and manage delirium at home. He also shared where his lab’s research into anti-inflammatory treatments currently stands.

Being Patient: Why do infections, especially urinary tract infections, have such a profound impact on cognition?

Dr. Shouri Lahiri: Infections often [trigger] an inflammatory response that emerges to combat the infection. That same inflammatory signaling can get into the bloodstream and induce changes to brain cells that manifest as delirium, an acute confusional state. 

We should probably first define delirium as a sudden disturbance in brain function that develops over hours or days and primarily affects a person’s ability to pay attention, remain alert, think clearly, and interact normally with the environment. One of its defining features is its fluctuation. A person may be perfectly cognitively intact at one point of the day, and several hours later, profoundly confused or withdrawn. 

When you have this inflammatory response that’s there to counteract the UTI, the infection in the bladder, we have shown in our lab that interleukin-6, for example, which is an inflammatory protein, gets into the bloodstream and induces injury to the brain cells and manifests this acute confusional state. 

Particularly in patients with dementia, who may have less physiologic or cognitive reserve, they’re more susceptible to this kind of unraveling effect. Whereas someone who’s younger and has a healthier brain would be more resistant or able to tolerate these inflammatory changes. What can present as fatigue in a younger person could present as an acute cognitive disturbance in someone older. 

Being Patient: Can frequent infections, particularly UTIs, have a longer-term impact on cognition? What do we know about that relationship and the potential long-term effects?

Lahiri: We have some information related to this. Certainly, UTIs, even in older populations — up to one-third of patients with UTI can develop delirium. It’s common a common complication for a condition that affects 400,000 people. It’s a very prevalent condition.

Other epidemiological, large-scale studies have shown that the number of delirium episodes a patient has in their 60s increases the risk of developing dementia proportionally. So, yes, there appears to be a possible causal link between delirium and dementia, and we know UTIs are common precipitants of delirium. In that sense, the UTI-to-dementia connection is there. 

We also know that delirium doubles the rate of cognitive decline in patients with dementia. Again, this is just clinical, epidemiological studies, but it certainly is consistent with clinical experience. 

The other point you had earlier, about the sudden, acute, dramatic change, is an important one, because delirium is pretty heterogeneous, meaning there are many ways it can present. You can have mild changes, confusion, hallucinations, even agitation, or you can be withdrawn, disengaged, or even hypoactive. There’s in fact a type of delirium called the hypoactive delirium phenotype, a condition where patients become withdrawn, disengaged, even sometimes comatose in very severe conditions. So, yes, we expect to see wide variability and dramatic changes in patients who develop delirium. 

We do feel that earlier, timely initiation of antibiotics is critical to recovering the cognitive symptoms, because antibiotics will clear the ongoing precipitant of the inflammatory response and help prevent ongoing brain dysfunction.

Being Patient: So for delirium — aside from treating the infections, is there anything people can do to prevent that?

Lahiri: There are some things folks can do. One is, again, early recognition and treatment of the precipitating cause. But one shouldn’t stop when they identify one source or one culprit — delirium is often multifactorial. 

Certain medications, like opiates and anticholinergic medications, along with a host of other drugs, are well known to precipitate delirium-like states. Hydration is very important, treating constipation, pain, or other metabolic changes — maybe alterations in certain laboratory findings. Early attention to these physiological and laboratory derangements can also help. 

The other thing is general housekeeping: maintaining an intact sleep-wake cycle. During the day, the curtains should be drawn, there should be light in the room, and the patient should be awake. Nighttime is when we sleep — we don’t want that to reverse. That sleep-wake cycle reversal can make things worse. If folks need hearing aids, those should be in. If they have eyeglasses, those too. Those are all environmental contributors to delirium that can be modified.

“There appears to be a possible causal link between delirium and dementia, and we know UTIs are common precipitants of delirium.”

Being Patient: We’re getting a question from a viewer, who’s asking: “If the UTI isn’t treated, will the delirium last until the UTI is cleared?”

Lahiri: It certainly can. In the worst cases, a UTI can lead to sepsis and even death — in fact, it’s a leading cause of mortality in patients with dementia. So yes, it can either progress or in some cases, I guess, it could self-resolve, but that should certainly be the expectation: earlier treatment is important.

In one study I read several years ago, I think it was that half of all patients with Alzheimer’s disease present to an emergency department every year, and the leading diagnosis on discharge is UTI. So, very common — and again, strongly associated with, or can lead to, sepsis if untreated, and mortality, a leading cause of death among patients with dementia. So yes, it can either continue, or things can get worse, or, rarely, it’ll get better on its own. But I wouldn’t count on that.

Being Patient: I think part of the challenge for caregivers is that it can be really difficult to get someone with dementia to the doctor and collect a urine sample, especially in the later stages. I remember caring for my mom and spending a long time in the bathroom with her just trying to get a sample.

If a caregiver notices a sudden or drastic change and suspects a UTI, what should they do? Are there reliable ways to test at home, or does someone need to see a doctor? What’s the best way for caregivers to find out whether a UTI could be causing that change?

Lahiri: This is a very tricky and controversial area. Often, another compounding factor is that patients who have severe or more advanced dementia may not even recognize the classic urinary tract infection symptoms, like burning with urination, abdominal discomfort, or urinary frequency. So eliciting — or even recognizing — a symptom of UTI is hard, and delirium may actually be one of the first presenting symptoms you’ll see. 

Often looking for things like grimacing during urination, repeatedly reaching for the genital area, a new change in continence, fever, or some other visible discomfort with the urinary tract could be a sign that this needs to be evaluated through laboratory testing. 

There are some over-the-counter, at-home tests to check for UTI, but probably the best thing to do is go to a doctor and describe the urinary symptoms, which would then indicate clearly that a urine sample needs to be taken. There are other ways to get urinary samples — sometimes even catheterizing the patient, clean catheterization, will elicit a urinary sample. So I would suggest going to the physician to get a sample, and going about it that way. 

Part of that is also because when you’re older, particularly postmenopausal women, you can often have bacteria colonizing the urinary tract, and even have inflammatory cells, but that doesn’t necessarily mean you have a UTI. So a UTI diagnosis is really linked to the symptoms of UTI — it is a clinical diagnosis. A urine test should support the clinical diagnosis; it should not replace one. If you treat with antibiotics injudiciously, it can lead to antibiotic resistance, or even other types of infections, like Clostridium difficile, which are problematic. So it does require clinical acumen and clinical diagnosis, but symptoms are a big part of the diagnostic criteria.

Being Patient: A viewer is commenting and asking: “My wife is still at home with me. During a UTI, my wife sometimes does not recognize me or is even afraid of me. Her normal state is confused and nonverbal, but the complete terror and clear lack of orientation to place and time is severe. Would taking an anti-inflammatory with the antibiotic be helpful if the cause is brain inflammation?” 

Lahiri: That’s a great question. The answer is maybe, but it’s not ready for prime time. My lab has a particular interest in this area, and we’re looking at several candidate drugs that would target the inflammatory system, but we need clinical trials before I can talk about what those are. Some of them relate to estrogen hormone signaling, but again, that’s not something I can say right now. 

I think in that particular case, I would say get ahead of the diagnosis and implement preventive measures: hygiene, bladder emptying, even maybe topical estrogen if it’s a recurrent situation — meaning estrogen over the genital area to reduce your rates of UTI. And then, if all else fails, oral antibiotics or even IV antibiotics are needed. 

In the future, we are working on drugs that can target downstream of the infection itself, more on the inflammatory response, maybe the IL-6 pathway, the interleukin-6 pathway, as we were discussing, but maybe even directly neuroprotective medications. So that’s hopefully coming in the future.

“What can present as fatigue in a younger person could present as an acute cognitive disturbance in someone older.”

Being Patient: This reminds me of something similar I saw when my mom had COVID. Her symptoms looked very different from what we typically think of with COVID. She suddenly couldn’t walk or talk, and the change was almost overnight.

We know COVID can affect the brain and trigger inflammation. Is there a similar relationship here, where an infection can cause a much more dramatic neurological or cognitive response in someone with dementia? Why might an infection like COVID affect a person with dementia so severely?

Lahiri: Yes, 100 percent. In fact, if you recall, COVID is a condition characterized by elevated interleukin-6 levels. So even without the virus or a bacteria entering the brain, just the inflammatory response alone can trigger these acute brain changes, like delirium, and other changes that you’re describing. 

We’ve previously published data showing that blocking the IL-6 pathway in COVID patients improves delirium phenotypes. It’s a retrospective study — I won’t get into the technical details — but we’ve published that data, and it’s consistent with our laboratory work, and also consistent with this inflammatory immune hypothesis, the immune-mediated brain injury hypothesis of delirium. And certainly, having pre-existing neurodegeneration — Alzheimer’s disease, dementia — is one of the strongest risk factors for delirium. So having that increases your risk further of having this acute delirium-like change. And yes, we believe that this is interleukin-6 mediated.

Being Patient: There are a lot of questions and comments about incontinence — because if you’re incontinent, you’re probably at more risk of UTIs, correct?

Lahiri: The short answer is yes. Incontinence, especially fecal incontinence, when there’s contamination of fecal material within the genital space, is certainly a setup for urinary tract infection.

Incontinence can also go hand in hand with bladder dysfunction. Take Parkinson’s disease, for example — it’s a neurodegenerative condition, but it also has something we call dysautonomia, or autonomic failure, and one of the features of dysautonomia is bladder retention. And that bladder retention — because you’re not emptying your bladder properly — can cause incontinence, but you can also have a buildup of urine in the bladder, what we call urinary stasis, where basically the urine’s not moving, and there’s an increased risk of infection. 

So, yes, incontinence can be a feature, as well as a consequence, of infection and neurodegeneration.

Being Patient: Are there any preventive measures — if a person is incontinent — that could help? You mentioned estrogen earlier in this conversation. Is there anything people could do to prevent or reduce the risk of UTIs?

Lahiri: There are treatments. Estrogen, topical estradiol, is probably the one that works best in minimizing the risk of urinary tract infection. In terms of incontinence, I think good bowel and bladder hygiene is important — regular emptying of the bladder, staying hydrated. 

In patients who have issues with dysautonomia or urinary retention, it’s sometimes necessary to escalate to things like clean catheterization, which patients with Parkinson’s disease sometimes end up needing, especially those with very severe autonomic failure as a feature of their disease. Those are the big ones.

There are other things people do as well, like methenamine and probiotics, and those have mixed data. But the one I think has the strongest data is topical estrogen, along with good bowel and bladder hygiene and regular emptying of the bladder when appropriate.

Being Patient: Finally, Dr. Lahiri, you mentioned your research on anti-inflammatories and whether they help when people are facing UTIs. When can we look forward to that research? Where are you in the study exactly?

Lahiri: As you can imagine, these are very complicated interventions to study in humans, so we had to start at a basic research level of analysis. We’ve shown now that estrogen — 17-beta estradiol, specifically — at least in basic research studies, helps prevent delirium in mice with UTI. 

We’re also now publishing data on another drug called bazedoxifene, which is used as an osteoporosis medicine but also targets both the IL-6 pathway and estrogen signaling in the brain, and may have some potential beneficial effects. 

What I’d say is that if there’s another indication, not related to delirium or UTI, where you and your doctor could have a discussion about whether hormone replacement or these drugs could be helpful, then it would be a way to kill two birds with one stone.

At this point, I can’t say this is something we should recommend routinely, because we don’t have the clinical studies — you need both basic research and clinical studies before you can do randomized, prospective clinical trials, before I can make definitive recommendations. But if there’s a dual indication, a different indication, it would be something that could perhaps tilt your hand toward it. So hopefully — clinical trials take a while — but hopefully in the coming months and years.