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BackTable / ENT / Podcast / Transcript #225
Podcast Transcript: Sinusitis & Cognitive Impairment: Exploring the Inflammatory Pathway
with Dr. Aria Jafari
Chronic sinusitis might be doing more than just clogging your nose–it could be clouding your brain. In this episode of Backtable ENT, Dr. Aria Jafari, an assistant professor at the University of Washington and co-director of the Neuroendocrinology Advanced Sinus and Skull-base Surgery Fellowship, discusses the connection between sinusitis and cognitive dysfunction with hosts Dr. Gopi Shah and Dr. Ashley Agan. You can read the full transcript below and listen to this episode here on BackTable.com.
Table of Contents
(1) Chronic Rhinosinusitis (CRS): Impact on Quality of Life
(2) Understanding “Brain Fog” in CRS
(3) Screening for Neurocognitive Dysfunction in CRS Patients
(4) Assessing Cognitive Interference: The Stroop Test
(5) Pathophysiology Linking CRS & Cognitive Dysfunction
(6) Patient History & Risk Factors in CRS-Related Cognitive Dysfunction
(7) Patient-Centered Treatment Strategies in CRS
(8) Advancing Neurocognitive Assessment & Management in CRS
(9) Take-Home Message for All ENT Physicians
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[Dr. Gopi Shah]
Hey, everybody, and welcome to the BackTable ENT Podcast. My name is Gopi Shah. I'm a pediatric ENT. I am across the mic with my co-host partner in this awesome endeavor, and dear friend, Dr. Ashley Agan. How are you?
[Dr. Ashley Agan]
Hello. Good morning. I'm so good and so excited. We're talking about sinusitis and cognition, and brain fog today, so if that's something that you've seen in your practice and you are curious about, then this is going to be the episode for you. We're very lucky to be joined by Dr. Aria Jafari. He's an assistant professor at the University of Washington and is the co-director of the NeuroRhinology Advanced Sinus and Skull Base Surgery Fellowship there. He's doing some really exciting research on sinusitis and cognitive dysfunction. Welcome to the show, Aria.
[Dr. Aria Jafari]
Thanks. Thanks very much. Good morning, Gopi and Ashley. It's great to be with you.
[Dr. Gopi Shah] Can you tell us a little bit about yourself and your practice?
[Dr. Aria Jafari]
Sure, I'd be happy to. I'm a West Coast native. I did my med school at Stanford and my residency at UC San Diego, then headed out east for my Rhinology and Endoscopic Skull Base Surgery Fellowship at Mass Eye and Ear in Boston. I've been in Seattle at the University of Washington ever since, going on five years now, where I practice the full spectrum of rhinology and endoscopic skull base surgery with some amazing folks here. I have a particular clinical interest in endoscopic orbital surgery and a research interest in outcomes with particular interest in cognitive outcomes in patients with sinonasal inflammation.
[Dr. Ashley Agan]
How did you find your way to that particular research, that kind of research? I guess, in my mind, a lot of things come from our experiences with patients and so I'm just imagining, as you're seeing patients, you're noticing, "Wait a minute, everybody's talking about brain fog. Why is everybody so out of it in my clinic?"
[laughter]
[Dr. Aria Jafari]
That's a good question. You're absolutely right. It all starts with your interaction with patients. For me, actually, I think the seed was planted probably in medical school, where I was trying to decide on a specialty. I had a strong interest in the neurosciences and was thinking about neurology in terms of a specialty or neurosurgery. I took an ENT rotation because I had to as part of the rotation package that I had to do for general surgery, and it was interesting in that experience. I think all of us can relate to this. I was just taken aback by the human experience that's associated with the conditions that we treat. I felt like the conditions were not just like a sinus condition, but like a whole-life condition. Being able to influence that or help patients navigate that seemed pretty powerful.
To be honest with you, I think that part of it went into the back burner as I dived deep into residency and residency training. Then, I think eventually, subconsciously, I got drawn back into it through Rhinology Fellowship. I think it wasn't until my fellowship year, where one of my fellowship mentors and my fellowship director, he had this way that he interacted with patients that was a little bit different than I had been used to. He taught us not just to ask about their sinuses, but to really ask and understand who the patients are and what they do for work, what their lives are like.
That deeper connection led patients sharing about how CRS was impacting them in ways that I didn't often think about. I was surprised by that and I started thinking more and more about that. Folks would share really intimate details about their lives, about how they were embarrassed on a Zoom call because people kept asking them if they were sick, or they weren't able to show affection to their partners because their nose was too stuffed up to kiss their spouse, or they're struggling to do basic tasks like paying bills, or they would forget their keys. It was something that I didn't really expect in a sinus clinic.
That's where it started. I started thinking about it more and I approached a mentor of mine in fellowship and I said, "Hey, I want to do a research project. It would be a research project that I had been more familiar with in the past, maybe an outcomes project or basic science project, or something like that." That particular mentor actually turned it back on to me and said, "Why don't you send me three research ideas? We'll review them together and we'll go from there." I sent two ideas that were more run-of-the-mill and then I threw this one idea that was totally off the wall.
I was like, "You know what? I think we should study patients with sinusitis and look at brain fMRI and see if there's a difference in brain activity because clearly the behaviors that patients are expressing, what they're experiencing is different." I thought he would say, "This is crazy. No way," but he said, "This is a great idea. We should do it." From there, he connected me with some amazing people, amazing collaborators at the Mass Eye and Ear and beyond and we were able to do one of the first functional imaging studies looking at how the brain can change in states of sinonasal inflammation. Anyways, it's a little bit of the journey and then since I've been here at the University of Washington, we've continued that in a lot of different ways and tried to study it as best we can.
(1) Chronic Rhinosinusitis (CRS): Impact on Quality of Life
[Dr. Ashley Agan]
I love that. So much serendipity in your story, just [laughs] so fun. As we start to talk about how sinusitis and brain function and cognition all intersect, can we just start by talking about things that you've alluded to with your patients, so overall quality of life impact for patients with CRS? Are we talking about all comers, CRS with polyps, without polyps? some mild mucosal thickening? Is it just in the elderly, like who is this and-- Yes.
[Dr. Aria Jafari]
Yes, it's a great question and, from my experience, it is all comers. It's the CRS with polyps. It's the CRS without polyps. It's the minimal disease patient. It's the maximal disease patient. It's the young patient. It's the old patient. It's the high-functioning patient. It's the patient who's struggling. I think it spans the spectrum of all the patients that I treat and, it's no surprise to a lot of us that CRS is super duper common, 10% to 15% of the population, but I think it's not just about being common, it's about how deeply it impacts the patient's lives. When you start–
All I do is nose and sinus disorders in my clinic and so I see this 20, 30 times a day, it's more than just a stuffy nose. Imagine having a cold that never goes away and that cold slowly invades every corner of your life. I think it's not surprising to me, maybe other folks who are listening in that when we look at quality of life impact and compare it to other common diseases like congestive heart failure, and COPD, and asthma, and Parkinson's disease, CRS is right on par with those. It highlights the fact that this is so, so, so impactful.
Another measure that I think is pretty helpful in terms of understanding what our patients are experiencing relative to other conditions is something called a health utility value. This is something that was introduced to me through Tim Smith and his group and his work in this topic. A health utility value is basically how people rate their own health on a scale of zero to one. One is perfect health. I was just surprised that the score for patients with CRS is 0.65. This is on par with end-stage renal disease on dialysis and Parkinson's disease. Again, I think it just highlights how deeply CRS can reach into every aspect of health. It's not just like a physical condition, but it's also like a mental and an emotional one too.
On top of that, we spend millions and millions of dollars, $10 billion a year managing it, perform half a million surgeries. The patients incur a huge cost in addition to what they experience. Financially, they can experience a loss of about $7,500 a year, higher in patients with nasal polyps. That's the cost of medications, lost work productivity, something called presenteeism, where you're at work, but you're underperforming, anyways, just a huge amount of expenditure and cost to society and patients themselves.
Anyways, yes, when I talk to patients, I always like to ask this question, which is-- Obviously we ask the cardinal symptoms, we ask facial pain and pressure, discolored nasal drainage, nasal obstruction, loss of sense of smell but I always like to ask, how is this condition affecting your life? I think you'd be really surprised to hear what people say. [chuckles] We hear poor sleep, fatigue, that comes up over and over again. We know that patients with CRS are twice as likely to have poor sleep and much more likely to be depressed, but increasingly and increasingly recognized this component called cognitive dysfunction or brain fog. That keeps coming up when I talk to patients and probe that.
I think that's really fascinating and I think requires a lot of our attention because it's really those non-nasal symptoms that drive patients to seek care, number one, but also to make medical decisions, specifically escalating treatment and deciding to undergo endoscopic sinus surgery. There was a really interesting study that showed that patients who have a higher psychological domain within the SNOT 22, which is the sino-nasal outcome test. If we look at the psychological and sleep components of that test, folks who tend to score higher on that dimension of it tend to elect surgery more so than folks who have a lower score on that. Anyways, I found that that's interesting and impactful and important for a lot of reasons, including how we treat patients and the treatments that we offer patients.
(2) Understanding “Brain Fog” in CRS
[Dr. Gopi Shah]
Aria, you have an example of a patient describing their symptoms to you specific to brain fog. Do you mind sharing that with us?
[Dr. Aria Jafari]
Cool. Yeah, no, this is a patient of mine that I actually met with last week. I knew I was going to be with you guys today and so I just asked if you'd be willing to share his experience with sinusitis and how it's been affecting his life. Yes, let's go ahead and play it.
[Patient]
I think the biggest issue when I do have these sinus infections or sinus issues beyond the congestion and the facial pain is really the brain fog really interferes with the daily life for me. It really puts me in a situation where I can feel it coming on. I really have a hard time concentrating and focusing on things. Yes, I think that's the biggest issue for me is where constantly you're fatigued. You're mentally fatigued for some reason. You're trying to figure it out and trying to work. I think it's one of the biggest impacts of the issue for me is the brain fog. Will it stop me from being productive?
I really have to slow things down, impact the way of me thinking. It slows my thinking capabilities quite a bit. I feel like in a separate person when I have the brain fog, that's the most interesting thing. Once I have it bad, you don't recognize yourself. You're kind of different. You're like, "What's going on?" It's one of the, probably, the only time of the year, where I take sick leave out of work. It's very interesting. It's the only time I get a sinus infection that affects my work like that. I also have a daughter. It affects me that in terms of interaction. You just don't feel yourself. I think it's the hardest thing to deal with.
[Dr. Gopi Shah]
There's so many things that your patient says where I'm like, oh, my God. It's like, yes, I get brain fog, but when he says, "Oh, I can feel it coming on. It slows my thinking," it affects him with his daughter, I'm like, wow, this is more than just the studies that you're like, oh, work, productivity, and those things that you just- like a checkbox. It's so much more profound.
[Dr. Aria Jafari]
Totally. Yes. It's like in one and a half minutes like you can learn so much about how this condition is affecting them. I think it was like, those questions were often a little uncomfortable to ask because we don't know what they're going to say, [chuckles] when it's beyond, like you said, the checkbox.
[Dr. Gopi Shah]
Runny nose. [laughs]
[Dr. Aria Jafari]
Runny nose. We're trying to make the diagnosis. We learn so, so much. Yes, there's things, like you mentioned, the mental exhaustion of it all. I think that really strikes me. That's a theme that I keep seeing with my patients. They're just-- It's so much at the forefront of their lives. Everything they do, they have to power through the brain fog first to do whatever they need to do. I think it's tiring and it's exhausting for a lot of them. It's important to recognize it. I think patients, they're just acknowledging that dimension of their condition is really powerful. I think people really feel heard. I think it's a nice way to just fully understand the impact.
[Dr. Gopi Shah]
How long does it last for? You have a patient with CRS, right? We're thinking this is now months of having sinonasal symptoms, weeks. The brain fog, is that something that comes and goes? Is that something that's around just this whole time?
[Dr. Ashley Agan]
Can we also define brain fog since it's more of a patient term than our term?
[Dr. Aria Jafari]
Absolutely. Yes, exactly. Brain fog is a colloquial term. I think there was a Reddit study that asked or reviewed Reddit posts and asked and they looked at posts that were looking at brain fog or mentioned brain fog. The most common themes that people described were things like forgetfulness and difficulty concentrating, cognitive slowness and problems with communication. It's really like an umbrella term as this describes a collection of symptoms rather than a single problem, again, difficulty with planning, organizing, making decisions, finding words, learning, remembering, and in even severe cases, it can affect personality. I think the clip that we played, I was surprised to hear he felt like he wasn't himself.
That's actually, again, a common theme that they feel like it's an out-of-body experience. They're not who they want to be or they typically are. They're not as sharp. They're not as witty. It can impact their relationships, their social interactions. They're not wanting to go out to dinner, interact with their friends. They're wanting to stay at home. Yes, I think that brain fog term is, like you said, an umbrella term, a little bit of an ill-defined term. Cognitive dysfunction is a little bit more specific because it discusses more precise brain networks, brain components that go into how we think or go about our daily lives.
Yes, I think it's important to know that not every patient with sinusitis has brain fog. [chuckles] That's one thing that I think we should just discuss off the bat. We did a study and about 50% of patients that come through our clinic who have a diagnosis of chronic rhinosinusitis end up having some form of at least mild cognitive dysfunction when they were administered a test. It's called the Neuro-QOL NIH Short Form 8-question Test. It's like a screening test. It has population norms and I was surprised to see half the patients actually were below the population norm for cognition. About one in six actually had severe cognitive dysfunction, which was one and a half standard deviations from the mean. That's a pretty impactful, pretty big number.
(3) Screening for Neurocognitive Dysfunction in CRS Patients
[Dr. Ashley Agan]
Is that test asking them, how well do you feel like you can do these tasks? Is it actually like giving them a test and making them think? You know what I mean? [laughs] Are there right and wrong answers on that test?
[Dr. Aria Jafari]
Yes. There's so many tests that test cognition. We incorporated this into our intake in our sinus clinic through a virtual format. We found that it wasn't something that needed to be administered by a research coordinator or anything like that. It's a Likert scale. It's one to five. It asks questions like, tell us how often this occurs. One of the questions is like, "My thinking is slowed. It seems like my brain is not working as well as usual. I have trouble concentrating. I have trouble adding and subtracting numbers in my head." Those are some of the questions that we ask. Yes, there's a lot of different tests that we administer.
We've done different types of tests, more like objective tests as well instead of subjective tests, where the patient reports it and more things that we're able to measure more objectively as well. This was just surprising to see the sheer number of patients who have trouble with this daily functioning. Then I also asked the question like, what about patients who just have nasal obstruction, their nose is blocked? Maybe they're seeking care. How do they do on this test? There's a decent amount of patients who also have a report cognitive dysfunction. About 10% of patients with obstructive pathology alone also have some sort of cognitive dysfunction. Overall, it's just much higher in these sinonasal patients than the average population.
[Dr. Gopi Shah]
For the neurocognitive screen that you did, you use it for research, but as well as to better understand what your patients are going through. Do you then ever use it to then refer to neurology or do you get functional MRIs as part of-- How do you then, if there is somebody that's really scoring or you're concerned-- I don't know what I'm trying to ask you, but, yes, what do I do with that information? When do I clinically–
[Dr. Ashley Agan]
Have to change management. [laughs]
[Dr. Gopi Shah]
Yes, or when do I clinically have to then include neurology?
[Dr. Aria Jafari]
Other specialists and things like that?
[Dr. Gopi Shah]
Yes.
[Dr. Aria Jafari]
Yes, totally. I think there's-- The screening test is one way to better understand folks and their cognitive ability, but even the SNOT-22, like I had mentioned, has domains that include questions about concentration and cognition. There's a psychological domain score that can be easily calculated. We also look at that to figure out, how much that component of the condition is contributing to the overall burden of disease. That also raises my suspicion for cognitive dysfunction, even if we weren't administering this screening test. I think you take all the information like we do, with any patient and we process it. I think if the condition is coincident with sinus flares or their sinus condition overall, I think that you can have a conversation with the patient and say, "Hey, does this ever get better or worse? Is this fluctuating?" similar questions that I think I ask my patients like smell loss. Is this something that's coincident with some of the other sinus conditions, symptoms that you have and does it ever get better with treatment like prednisone or nasal irrigation or that kind of thing? If they say, "Oh, yes. When I'm feeling good, I'm totally sharp. I'm ready to go. I'm at work. I'm on top of my game. When these symptoms flare up, I really feel it."
To me, I feel like that is probably more connected to the sinus condition and I think can be managed by us as otolaryngologists. I think if this cognitive dysfunction is significant, I dig a little deeper. I ask about tremors and memory loss and weakness or other neurologic changes. Of course, if there's anything there, then I would refer to a neurologist and help them figure out if there's a separate neurodegenerative process going on.
[Dr. Gopi Shah]
I would assume that's pretty rare. You're probably not diagnosing a ton of neurodegenerative problems, right?
[Dr. Aria Jafari]
Right. Yes. I would say once a year maybe I come across a patient, where they have something more concerning or worrisome and I'd have to send them to neurology for formal neuropsychiatric testing. What's cool is the neurologists actually know that we're doing some of this work and so I actually get more referrals in the other direction, which is surprising. You would never think a neurologist would refer to a sinus surgeon.
[Dr. Ashley Agan]
They're like, "Rule out sinusitis." [laughs]
[Dr. Aria Jafari]
So funny. Yes. No, they get tons of imaging and they get, the polyps are coming, all over in the MRI scan, then they're like, "Hey, maybe we should check this out." They kick it back to us. I actually think the referrals come from the other direction. [laughter]
(4) Assessing Cognitive Interference: The Stroop Test
[Dr. Gopi Shah]
That's a great partnership. Before we moved past, talking about tests, you had sent us an example of the Stroop test. Basically- or I'll let you describe what this, what this test is.
[Dr. Aria Jafari]
Yes. Yes, we were just talking about neuropsychiatric testing. Among the battery of neuropsychiatric tests, one of the oldest tests that neuropsychologists administer to patients is something called the Stroop test. It tests interference so if you have a distractor in your environment, how much are you able to focus on the task at hand and to execute the task at hand while you're distracted by something else.
[Dr. Ashley Agan]
Basically, the Stroop test is every day in my house.
[Dr. Aria Jafari]
[laughs]
[Dr. Ashley Agan]
It's like every day.
[Dr. Aria Jafari]
Well, actually, yes--
[Dr. Ashley Agan]
Real life. Yes.
[Dr. Aria Jafari]
It's, exactly, trying to emulate real world--
[Dr. Ashley Agan]
I'm just going to tell my kids, "Yell more. Yell more." I got to make sure I can't finish this task. It's challenging my mind here, so it's good. [chuckles]
[Dr. Aria Jafari]
Yes. What's interesting is the sinus patients actually do overall okay on basic tasks. I think that's also important to know. We're not-- These patients aren't having a significant amount of reaction time issues or a more of like the simple types of tasks. They're actually having issues with a little bit more of like the higher level tasks which require more attention or more brain function. Stroop tests that. Folks at MUSC administered this test to their patients and they wanted to see the impact of medical therapy on cognitive dysfunction in chronic rhinosinusitis.
They found that the reaction test, the Stroop reaction test, which is basically a series of words that are in colors, there'll be like a red word, it'll say red, but it'll be in red color and then there'll be like a green word and it'll be in green and then they'll administer that and then they'll administer the same words, but the colors will be switched in the words. It'll be listed as green, but it'll be red and they'll ask the patient to say the color and not the word. They found that patients with chronic sinusitis actually struggled with that because it's hard for them to get past the fact that the word green is actually in red color. That actually was interestingly also something that improved with medical treatments.
[Dr. Gopi Shah]
They're just checking to see if they get it right. Is it timed? Do you need to be able to do it fast? Because as I'm sitting here looking at it, I have it pulled up and–
[Dr. Ashley Agan]
Green, red, blue.
[Dr. Gopi Shah]
[laughs] If I take my time, I'm like, "Okay, red, green, yellow, blue"-
[Dr. Aria Jafari]
Yes. It's a time thing.
[Dr. Gopi Shah]
-but if I tried to go faster, I think I would miss more-
[Dr. Aria Jafari]
Totally, yes. Yes.
[Dr. Gopi Shah]
-or slows down after three. I'm like, "Oh God, come on. Come on."
[Dr. Aria Jafari]
It's a tough test actually. It's super tough. Yes, it's a timed thing. They'll time it. Then if it takes longer to get it, then they'll record that.
[Dr. Gopi Shah]
These things are fun because it's interesting to see how your brain tries to just do things faster or to do things without thinking. Then it's like the wrong thing or-- Similar to those paragraphs where they leave out, most of the word, but if it has the first letter and the last letter, your brain will just fill it in and read it. It's just fascinating. Yes, super fun.
(5) Pathophysiology Linking CRS & Cognitive Dysfunction
[Dr. Ashley Agan]
Do we understand any of the pathophysiology? Is there a pathophysiology or, something now that we're saying, "Hey, there's a link here. Do we know why?"
[Dr. Aria Jafari]
Yes. That's a great question. I think the honest answer is probably we don't fully know yet, but we have some strong theories. I think the two leading ideas are one, could this be like a neurodegenerative process? Are we speeding up Alzheimer's disease or something like that? Is chronic inflammation causing neurodegeneration? Then the second theory or idea is chronic inflammation, triggering neuro-hormonal changes that affect cognition. I would say that the preponderance of evidence actually supports the second theory, which is that there's like a neuro-hormonal change that changed the milieu within the brain and changes the brain functioning based on the inflammatory response that is present in CRS, but also many other conditions.
We did a study and we looked at neurodegenerative markers and spinal fluid in patients who had sinus inflammation and we didn't see any difference. That supports the fact that, it's probably not cell death. It's probably just dysregulation. Clinically, we also see that, like I had mentioned, the patients like will fluctuate in terms of the severity of their cognitive fog. That's usually coincident with the level of inflammation. What is neuroimmune or neuro-hormonal? What does that pathway look like?
Well, I think we all experience it and know it on a personal level. Like if you cut your skin with a paper cut, it feels warm. It could be tender. Those are inflammatory cytokines that rush to the site to help us, to help us heal. In CRS, we know that there are cytokines like IL-1, IL-4, IL-6, tons of cytokines. They feed signals actually back to the brain to regulate the immune process.
Cytokines aren't just these factors that cause physical symptoms like fever and body aches and redness, that kind of thing. They actually are increasingly known to cause behavioral changes and that's called sickness behavior. If you ever had like a bad cold or a flu, you know what that means, right? You don't want to do much. You want to hang out at home, maybe not socialize. It's actually an evolutionary adaptation, we think.
When your body is fighting an infection, it wants to conserve energy. We only have like a certain amount of energy and calories. Your body like turns everything down in terms of the non-essential activities, including higher cognitive processes. If you think about the last time you were sick, you probably felt withdrawn or tired, you had trouble concentrating and maybe felt a little depressed. That's actually your immune system deliberately influencing your brain to prioritize your healing.
It's crazy because I always thought blood-brain barrier in medical school, but turns out there's more of a communication than we think. The immune system communicates with the brain through structures like the choroid plexus. It's like this fluffy material within the ventricles and it regulates what can pass. One of the things that can pass is actually cytokines. When inflammation is prolonged, like it is in sinusitis, but also things like inflammatory bowel disease, or even obstructive sleep apnea, when it becomes this persistent state, the inflammation and the cytokines can actually influence the neural signaling within the brain.
There's even animal studies that back this up. I think, I don't know, this is a funny one, but at a basic level tells me that there's probably some component of our immune system that influence our behavior. Reptiles, there's a study of iguanas, and every time they get sick, they seek out sunlight to raise their body temperature because they're cold-blooded. That's just at a basic level. It's like their behavior is changing to promote their survival. I think for us and states of chronic sinus inflammation, that's also happening, which is crazy.
[Dr. Gopi Shah]
These cytokines are probably traveling to the brain through the bloodstream. Because if it's happening in IBD and other things, it's not necessarily because the sinuses are-
[Dr. Aria Jafari]
Were that-- Yes.
[Dr. Gopi Shah]
-close to the brain. [laughs] It's traveling through the bloodstream and affecting behavior in that way, maybe.
[Dr. Aria Jafari]
Yes, totally. Exactly. That's what we think. Yes, things like sarcoidosis, they found that if you treat it medically with TNF-alpha, it improves disease control, but it also improves cognitive function. Then in conditions like sickle cell anemia, where the sickled cells trigger an inflammatory cascade, the increased levels of interleukins correlate with the disease, the inflammatory state, but also the cognitive functioning of those patients. Again, inflammatory bowel disease is the same thing. It actually is probably through the bloodstream and not like a direct effect.
[Dr. Ashley Agan]
Have we found any links between a patient on biologics? I would imagine if I'm on biologics for nasal polyps, I'm going to feel better because my nose and sinuses have less inflammatory mucosal disease. I can breathe better, but do the biologics affect the cytokines in my brain to then make that neuro-hormonal shift that may have occurred with my brain fog go back to the baseline? Are we seeing that?
[Dr. Aria Jafari]
It's a great question. I think I don't know of any studies that have specifically looked at that. Thanks for the idea, but it would make sense, right? We're directly impacting these signals and so we would expect that the brain fog would improve. I do know that when we look at quality of life overall, the SNOT-22 I know is a commonly used measure of disease control and studies that have looked at biologics, dupilumab and others, obviously patients are improving quite a bit on their SNOT-22. If it's particularly dramatic in certain domains or in cognition, actually, I don't know the answer to that, but it'd be interesting to further dive into it.
[Dr. Gopi Shah]
You did the study with functional MRIs, which are more looking at activity, but the brain essentially looks the same. You're not seeing long-term brain changes. It's just the brain is functionally working differently because of these inflammatory mediators.
[Dr. Aria Jafari]
Yes, exactly. Yes, then the brain isn't like-- We don't think that there's a degenerative process. We just think that the networks are just firing differently in the states of chronic inflammation and more shifting towards that introspective, what we call, the default mode, where you're self-ruminating. Those connections are actually strengthened. Then the connections to, what we call, the salience network, which is being alert and ready to act, those are decreased. The connections to those brain areas are decreased.
(6) Patient History & Risk Factors in CRS-Related Cognitive Dysfunction
[Dr. Gopi Shah]
Now, sorry, going back to risk factors, I know we're at the testing and how it fits, but patients who have like a history of OSA or depression, and now they have like CRS, are those patients going to be at higher risk for having cognitive dysfunction? How do you know it's the CRS that's worsening their baseline?
[Dr. Ashley Agan]
They have multiple reasons, multiple hits. [laughs]
[Dr. Gopi Shah]
Yes, exactly. How do I know? Maybe it doesn't matter because maybe if I'm rinsing my nose and clearing my sinuses, I'm overall feeling better. I don't know. How do you think about that?
[Dr. Aria Jafari]
It's a tough question. Right now, I think we don't know a lot about the specific risk factors for cognitive dysfunction and CRS. Part of the challenge is we don't really fully understand the immunology of CRS to begin with and we also don't really understand cognition to begin with. It's two things that we don't really fully understand and it's still a black box in many ways. Combining the two makes it even more complex.
I think one of the things that has borne out in our literature time and time again is the level of inflammation. It can probably put you at a greater risk for cognitive dysfunction. That's because the studies have shown that chronic rhinosinusitis with nasal polyps are primarily driving a lot of the cognitive effects and those patients we think of as having a more significant amount of inflammation in the nose and it fits with the overall theory of why we think this is going on.
To answer your question about other risk factors, I used to think maybe it was folks who didn't have a lot of cognitive reserve. There's been some studies on high IQ patients who are able to compensate for neurodegenerative issues or traumatic brain injury. My experience actually doesn't seem to fit with the cognitive dysfunction seen in chronic sinusitis. The clip that we played earlier was a patient of mine. He's an executive, and actually, he's performing at a high level all the time. When it dips just like, 1%, 5%, he's feeling it. He can't perform at that level.
I'm not quite sure if the cognitive reserve theory about compensation actually applies to this patient population because our patients are so typically high functioning, usually middle-aged, working, and they feel it more because they have to be on top of their game to function and be present at work. Yes, and I had mentioned, patients with chronic nasal obstruction, which we study, also have some cognitive dysfunction at a much lower level. There may be some component there that is contributing.
One of the really surprising findings when I was doing this research and trying to understand similar conditions that had similar patterns of cognitive dysfunction was obstructive sleep apnea, which turns out is actually a chronic inflammatory state as well. Those patients also experience cognitive dysfunction. This is all layered in by, the sleep disturbance. Many of these studies have actually corrected for hours of sleep or sleep quality and they still see the cognitive dysfunction borne out. It's because that the immunologic basis actually disrupts sleep centers as well. It's all interrelated, interconnected. It's tough to figure out, specifics in terms of risk factors, but I think, overall, it's probably our high inflammatory burden patients that bear the brunt of it.
[Dr. Ashley Agan]
Yes. That makes sense. Do the patients with CRS who have olfactory symptoms have a higher risk of having "brain fog or cognitive dysfunction"? Have you noticed anything like that? I just think of anosmia as an early sign of potentially Alzheimer's, right? That's realizing that I know that by itself is different than CRS, but smell and olfaction plays a role in CRS too.
[Dr. Aria Jafari]
Yes, totally. I think, obviously, smell loss has gained a lot of attention, through the COVID pandemic and that's borne out a lot of really interesting research to help us better understand the relationship. One of the really fascinating things that I love about the olfactory nerve is the only cranial nerve that interacts with the external world. It's in our nose and it transmits it directly to our brains and it bypasses the brainstem. We can learn a lot about that processing.
We don't think that inflammation in the nose is traveling in that direction through that nerve. Again, we don't know for sure yet. We do know that inflammation can shut down that nerve. We know that when that nerve is shut down, our brain is deprived of that sensory input. Similar to hearing loss and there's sensory deprivation that can affect cognition potentially. There's the sensory deprivation hypothesis, the idea that losing some sort of sensory input like smell can cause downstream degeneration in brain areas that depend on that input. I think it's probably two separate processes and not directly related and not as simple as going from the nose to the brain through that mechanism.
[Dr. Gopi Shah]
Also patients that are having anosmia probably have a higher disease burden if they have that many-- It goes along with your point earlier that it seems to be, patients who have more inflammation, higher disease burden maybe are more likely to have the cognitive dysfunction piece.
[Dr. Aria Jafari]
I think the duration also matters, something that we haven't chatted about yet. Folks who have had inflammation for a longer period of time tend to have worse cognitive dysfunction and that's been shown in other studies as well.
(7) Patient-Centered Treatment Strategies in CRS
[Dr. Gopi Shah]
As we think about taking care of these patients, treatment, whether it be medical, surgical, combination, biologics, all the things in our tool belt, do we expect patients to have, I assume you probably do like pre and post and you're following their cognitive function. What are you seeing in that regards? Is it usually, you had mentioned, fluctuating symptoms earlier? If we can get things under control, can we promise patients that they can be brain fog-free? [laughs]
[Dr. Aria Jafari]
Yes, I think I always like to see how patients respond to medical treatment and if their symptoms are going to respond to steroids or intranasal steroids or oral steroids, I tend to think that maybe good control over the condition overall through surgical treatment or biologic treatment or whatever we're offering them, will also have a similar benefit if it's truly related to underlying inflammation. We have that conversation together. I think that, yes, if they have strong benefit from the anti-inflammatory treatment, then the patient will have-- It's more likely that treating them with surgery or medical treatment in general will improve their cognitive functioning.
I think that this all plays into this X factor that I think about in sinus patients where we have the diagnosis, working at a teaching hospital and we have residents and fellows, often they'll see my patients in the clinic, they'll go in and get a history and do an exam and they'll come back and I'll always ask, what do you want to do? How do we want to treat this patient?
We always have a guess when we go in, but sometimes when we go in, based on what the patient tells us, that treatment plan completely changes, right? They're like, there's polyps coming out the nose, but they're not bothered by it at all. Okay, we're going to do something completely different. A lot of this is guided by the patient, how much it's affecting them, how much this condition is shaping their everyday life.
I will say, in general, if cognitive dysfunction is part of their symptomatology in a significant way it often pushes me to escalate medical therapy sooner and if needed, offer surgery to regain better control over their disease.
[Dr. Gopi Shah]
Does that mean you're more likely to do budesonide rinses or oral steroid burst versus like if you're going to, when you say offer medical therapy sooner?
[Dr. Aria Jafari]
Yes, exactly. Exactly right. I'm much more likely to offer a steroid burst and budesonide irrigations and maybe even convert or offer surgery sooner maybe than another patient that's not so bothered by that.
[Dr. Gopi Shah]
You'll have patients who get better with their sinonasal, the classic sinus symptoms, and the brain fog. Then you'll have patients that maybe they don't respond with the sinus or the brain fog symptoms. What do you do with the patients that the sinonasal symptoms get better, their polyps are better, but they still have this brain fog? Do you get patients like that? For us, seeing objectives, pus, swelling, pulse, we're like, okay, I have something to-- The brain fog, I think, I guess maybe because--
[Dr. Aria Jafari]
It's harder to see. Yes.
[Dr. Gopi Shah]
Yes.
[Dr. Aria Jafari]
Absolutely. Yes, I think those are the patients that we start thinking about something else going on, honestly. Those are the neurology patients where we'll collaborate with the neurologist to get their symptoms under better control or better understand or characterize their symptoms. I think the sinusitis can really cloud the brain fog symptoms in those patients. Often, they're much better, but they may not be where they want to be in terms of their cognitive symptoms. We'll have to collaborate with the neurologist to get a better sense of what's going on.
Interestingly, practicing in Seattle, I see a lot of patients who often seek like complimentary care through like naturopathy or acupuncture. I've actually learned about a lot of adjunctive treatments that treat brain fog, like acetyl-L-carnitine, which has actually reasonable evidence to support cognition. Acupuncture, I think there was a recent Nature paper that showed that it may help autonomic nervous system function and potentially help this patient group. It's like all hands-on deck effort if they're in that small group of patients who are still looking for more benefit.
(8) Advancing Neurocognitive Assessment & Management in CRS
[Dr. Ashley Agan]
What's on the horizon? What are we going to learn in the next 5 to 10 years about our sinusitis and our cognition?
[Dr. Aria Jafari]
Yes.
[Dr. Ashley Agan]
What studies do you want to, do you want to be seen or do you want to do?
[Dr. Aria Jafari]
Want to do. Yes.
[Dr. Ashley Agan]
Yes.
[Dr. Aria Jafari]
I think one of the main things that is holding us back right now is that a lot of our measures are subjective. We're asking patients to fill out a questionnaire. If someone is feeling miserable, they may fill out a questionnaire a certain way. Our SNOT-22 scores tend to track with our cognitive testing scores, especially when they're administered to the patient to self-report their condition. I think I'd like to see more objective data, more objective research, shifting away from cognitive testing and questionnaire-based assessments, but maybe more towards what we've been doing recently, which is eye movement testing, which is a low cost and a non-invasive way to assess integrity of brain circuitry.
Our eyes and our brain are super tightly connected and our attention is actually often very well measured by where we look. We've used it in our research recently where we showed that CRS patients who have significant sinus inflammation compared to controls, they have deficits in terms of eye movements and attention. We used different paradigms to assess that within that patient population. I think more studies like that, I think that was like a CRS patient population versus control. I think it'd be really interesting to look at the CRS patients, treat them, whether it's surgery or medical treatment, and then retest those same patients using eye tracking and eye movement assessments.
I think functional neuroimaging can be super helpful in this space as well. I'd love to collaborate with experts in functional neuroimaging. It's really exciting, but it's also really expensive. If anyone's interested in listening, reach out, we're happy to collaborate. It's tough because neuroscience and this type of work, we can't just go in and like sample their brain or, even doing CSF sampling is super invasive. We do have to find these surrogate tests to better understand what's going on.
[Dr. Ashley Agan]
With those eye movement tests, are you wearing the same goggles that they use for vestibular testing and the patient is tracking a dot on the screen or what is it?
[Dr. Aria Jafari]
It's exactly the same. Yes, I've collaborated with our vestibular scientists and we use infrared eye trackers. They're tracking a dot. There's four paradigms that we looked at, one that's called like the prosaccade. There's like a dot in the middle and then a dot appears, off to the side and then you just shift your attention. Then there's something called the anti-saccade where the same thing happens, but the instructions are that you look opposite the dot. That's a little bit of a tougher test. CRS patients tend to do worse with that test.
Then there's different variations of that we are able to assess cognitive functioning. Yes, we wheel that machine into our clinic and we pull patients in and do that test. It takes about 30 minutes or so. At the same time, we do some other cognitive testing with them. I'd like to follow those patients more longitudinally to better understand the impact of treatment on the functioning.
I think there's also some other interesting, super cool ideas that have come out in the literature, I think, what do we do about this. I think folks who are listening may be like, "Okay, great. I have a patient with CRS. They have cognitive dysfunction. Maybe I'll do some prednisone or, if they don't get better, what other options do I have?" I wonder if approaching this, approaching the neurocognitive component to CRS in a different way, in addition to our classic sinus treatments, could offer additional quality of life benefits, things like cognitive behavioral therapy or antidepressants or herbal supplements, I mentioned acetyl-L-carnitine. It'd be cool to see if those patients do better after surgery because we're specifically addressing that dimension of their experience.
(9) Take-Home Message for All ENT Physicians
[Dr. Ashley Agan]
Yes. I was going to ask you, what would be your take-home point for all the ENTs listening? I think that's, to your point, for me and preparing for this and thinking about it, I think that the big thing is just having a better understanding of the quality of life aspect to it because we're talking about lots of lost hours of not only productivity, but your patient talking about just time with their family and it can be a really big problem for patients. Just understanding how big of an impact it can be.
[Dr. Aria Jafari]
Absolutely. Yes, CRS is more than a nose disease. It's like a whole-life disease. That's one of the, I think, main things that I've learned doing this work, and brain health is sinus health. They're all interconnected. We talked about and asking simple questions, like how is this affecting your life can really help you understand the condition. If we ask the right questions, we recognize the hidden battles of our patients and what they're fighting and treat beyond what we can see on a CT scan. I think we can not just help them breathe better, but we might be able to help them live better too.
[Dr. Gopi Shah]
Well, thank you so much, Aria. I feel like the-- I was going to ask you, do you have any final pearls? The big pearl in the beginning for me was, when you said basically what is the human experience for the conditions that we treat. That's so beautifully put. As we rounded out, is there any other, do you want to add another pearl at the end? Is there anything else that you'd like to include?
[Dr. Aria Jafari]
First of all, thanks for having me on. This has been great, but I think it just is important to recognize that inflammation doesn't just stuff up your nose. It like rewires your brain. I think the more we understand how the brain and inflammation is connected to each other, I think the more we'll understand that this condition actually is a whole-body condition and a whole-life disease. I think that that's something that I hope that folks who are listening in will appreciate. I think we already appreciate that when we talk to these patients, but recognizing it as a real thing and telling patients that this is something that is a component of the condition and making sure they're heard can be really powerful.
[Dr. Ashley Agan]
Very good. Great.
[Dr. Gopi Shah]
[crosstalk] Do you have any, if people want to learn more about you or reach out to you, are you on social media or do you have a website or--
[Dr. Aria Jafari]
Yes, I'm on X, and LinkedIn, and Doximity, the typical social media sites, but I'm also, you can easily find me on the University of Washington, otolaryngology website. I think my email address is there as well. Happy to talk to anyone who's interested in this work. It's been a journey and it's been fun to talk about it with you guys.
Podcast Contributors
Cite This Podcast
BackTable, LLC (Producer). (2025, June 2). Ep. 225 – Sinusitis & Cognitive Impairment: Exploring the Inflammatory Pathway [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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