Long COVID and Its Effect on Cognition

Dr. Nathaniel Chin: Welcome back to Dementia  Matters. Today I’m joined by Dr. Jim Jackson, a research professor at Vanderbilt University.  Dr. Jackson is the director of behavioral health of the ICU Recovery Center and the lead  psychologist for the Critical Illness,

Brain Dysfunction and Survivorship Center  at Vanderbilt. His work typically focuses on chronic illness and Post-Intensive Care  Syndrome (PICS), but, after seeing how COVID-19 was affecting individuals long-term,  he has shifted to studying the effects of long COVID on the brain. Since then, he’s been  working on numerous studies surrounding long COVID and has published a book, Clearing  the Fog: From Surviving to Thriving with Long

COVID. Dr. Jackson, welcome to Dementia Matters. Dr. Jim Jackson: Dementia does matter, and it's really great to be with you today. Thank you. Chin: And I know you're able to speak to this whole spectrum, but for our purposes today,  let's speak to the older adult. So, to begin, what got you into the field of critical illness,  and then what led to you studying long COVID, especially its effects on cognition? Jackson: You know, it's such an interesting

question. I have a lot of mentees,  like you may, that I interact with, and they talk about career development, and they  often talk about it like it's a linear path. But I think it's anything but a linear path, and I  think sometimes you just find yourself in a place, and there's a lot of serendipity, and good things  happen. For me, that's really my story. I came to

the Vanderbilt VA Psychology Consortium from a  school in California. I had a lot of interest in neuropsychology and rehabilitation, health  psychology, etc. During that year, I met a man who's now become a close friend and colleague,  Wes Ely. He was a few years older than I, a few years farther in his development, and he had  this idea that—he's an intensive care doctor—he had this idea that intensive care patients were  perhaps surviving the ICU, and medically they were

perhaps fine but cognitively they perhaps were  anything but fine. He wanted to study that and I just happened to be the psychologist that was kind  of in the room. It was really that simple. I liked him, he liked me, and he said, "Would you like  a job? We'll pay you $50,000," which, in 2001, seemed like a lot of money. And I said, "Sold!"  It was that simple, and the timing was good. So much of success, I think, is about timing, and  we just happened to be kind of on the tip of the

spear. We were the first people, really, among a  few others, asking these questions about cognitive outcomes after debilitating critical illness.  There was a colleague, a close friend of mine, Dr. Mona Hopkins from Brigham Young. We were the  only ones, she and I and Wes, and it was really a

situation where we pulled a string and the story  started to really unravel. We began to really understand—not surprisingly now—that critical  illness–being on a ventilator, having issues with delirium, having enough sedatives to knock  a horse out–we began to understand that that, along with inflammation, was harmful to the brain.  In those days, people didn't believe it. I worked as an expert witness occasionally on cases, and  the opposing psychologist would say things like,

"I don't think sepsis really is harmful to the  brain. I don't really think critical illness is harmful to the brain." Of course now we know  it's incredibly deleterious to the brain, and so that's really my background. That's my story. Chin: So luck and timing. I have a lot of professors and mentees come on the show, Jim,  and I'll say they echo some of your sentiments. But I think an important ingredient is your  willingness and ability to take on the next

challenge. And so, your willingness to say yes. Jackson: You've got to be willing to jump in the deep end of the pool, right? And I did. In the  early days, we would start these studies, and Wes–Wes Ely, Dr. Ely–would say, "Jim, do you know  how to do X Y Z? Do you know how to put a battery together? Do you know how to do a cognitive  assessment for mild cognitive impairment?" I would say yes, and then I'd run to my office, I’d find  someone on PubMed, I would call them on the phone,

and they would tell me. I'm being a little  self-deprecating, but it was a lot like this. I think your point is right. You have to be  willing and you've got to do the work, right? You've got to do the work and it's hard work, but  it's really gratifying. Our goal in research has

been to impact the lives of people, even those  we never meet, right? And that idea—that you can perhaps transform some aspects of medicine or  generate some new knowledge that is not only going to help people in your immediate sphere but that  it is going to impact people around the world that you've never met—that's animating and motivating,  and that gets me out of bed every morning.

is COVID, and on the heels of that, they develop  brand new problems they didn't have before. Those problems are persisting—that's why we call it long  COVID. Typically, when we think of long COVID, those problems are persisting for two months or  three months, four months—something like that. They haven't gone away. They may not be getting  worse, but they haven't gone away. And that, in effect, is long COVID. It's a little bit  hard to talk about long COVID because often

we talk about it as if it is a thing—as  if it is a single thing. The problem, I think, is it's a multi-faceted, complex  thing. It's a lot of things. For instance, we see some people with long COVID–in quotes  “long COVID”–they have cognitive problems only. Some people have fatigue only. Some people have  mental health challenges only, balance problems only. Some people have the whole shebang and  everything in between. We have some limitations,

I think, to the language, to the term long  COVID. It's not very scientific. I think an equal challenge exists with the term brain fog,  which people kick around a lot, right? I think if you went to a medical center, whether it is the  excellent University of Wisconsin Medical Center or Vanderbilt or wherever it would be, and find  10 neurologists, ask them how to define brain fog, you're going to get about eight and a half  different answers. Whether it's long COVID

or brain fog, we need a little more precision. Chin: Well, given the work you do in post-acute illness, does long COVID present itself  similarly to these other diseases and, if so, how? Or how is it different? Jackson: I think it's quite similar, and you know, this is hotly debated: is it completely new? Is  it some version of things that we've seen before in terms of how it presents? It’s hotly debated. I  think what's unappreciated a lot is the idea that

there are a lot of acute illnesses. There are a  lot of post-viral syndromes that do have cognitive consequences. They present with cognitive  challenges. If we take the flu, for instance–if we look at the flu, we've studied people who have  been hospitalized with the flu, and in some cases, in the ICU with the flu. Not surprisingly  to me, maybe surprisingly to some of your guests—or some of your listeners, rather—but  not surprisingly to me, people after the flu

often have persistent cognitive problems. Now  they're usually fairly mild, often they go away, but that happens after the flu. That happens after  being hospitalized without the flu in some cases, right? It happens to so many people. Sometimes  it's a function of actual neurologic phenomena at work; sometimes it's a function of the impact  of anxiety and depression on cognition, right, which can masquerade as a brain injury, let's say,  and sometimes it's due to the effects of things

like inflammation. I'm not sure long COVID is as  different in the cognitive arena as people think. I think it's pretty similar to other things. Chin: And those other things—in your book, you talk about potentially a similarity with  chronic fatigue syndrome, which I think many people know, and, of course in our neck  of the woods, Lyme disease or having these persistent symptoms after Lyme. Do you  feel like there is a shared underlying

mechanism or process, and is that inflammation? Jackson: Yeah, I think that's right. I think it likely is inflammation, and the clinical  presentation is certainly the same. It's interesting. I get a lot of emails—well, I  got a lot of emails before writing the book, but since writing the book, I mean, they just  come. You know, they just come. I got one not long ago from someone who said they really loved  the book, and I was encouraged and all of that,

and they said, "You know, I never had COVID. I had  Lyme disease." And so, I think a lot of the people that have been impacted by the book are people  with chronic illness that may not have been COVID necessarily, may not have been long COVID—long  Lyme, chronic fatigue—but the presentations are so similar. They're really similar in some  ways to brain injuries in that, as you know, dementia percolates slowly, right? It kind of  develops slowly over time. Usually, if we think

of Alzheimer's disease it's a problem of memory  before it is anything else. When you look at the cognitive issues and the patterns of long COVID,  it's not a slow burn. It is quite abrupt. Often there is some improvement that doesn't tend to  involve memory as much as it involves attention, processing speed and some executive functioning.  I think the Alzheimer's analogy exists in some older, frail, vulnerable patients that we see  who likely already had a candle that was lit,

if you will. That problem is accelerated greatly  but brain injuries are a great model for what happens to long COVID patients cognitively. Chin: Jim, that was my next question. This idea of what are the common symptoms when it  comes to cognition that go with long COVID. You just mentioned some of the cognitive domains,  and if there are others, please share with us, especially for the older adult. What do people  tend to present with or notice when it comes

to their thinking ability? Jackson: If you remember, and I'm dating myself here, but when the war in  Iraq unfolded—of course, I work at the VA a bit, so I'm familiar with all of this—eople started  talking about TBI, mTBI, being the signature injury of the war in Iraq, and indeed it probably  was. I think one of the signature injuries, if we want to use that language, of long COVID  is deficits, in particular, in processing speed

and attention. Those are the areas where, when we  do cognitive testing, when we really drill down, people are most reliably affected and impaired.  What’s confusing often is, when patients come to see you—and of course this isn't unique to  long COVID—they complain of memory problems, right? It can throw you off a little bit,  especially if you're an internist or in primary

care because you may not be quite as savvy in this  neurologic space. While people are being sincere, they’re conflating memory with what I would call  processing speed or what I would call attention. When we drill down, we don't see a lot of amnestic  deficits in people per se; we see some working memory deficits, and when people get cognitive  rehab—as so many of our patients do for deficits in attention and processing speed—they usually  do so much better, and that's been one really

encouraging finding during this hard season. Chin: When you mention inflammation, and even a similarity with traumatic brain injury, do we know the underlying mechanism or how  exactly long COVID is damaging the brain, or if it's permanently damaging the brain or not? Jackson: I'm not sure we know exactly what the underlying mechanism is. In our ICU survivors who  had COVID, it's a little more straightforward to

understand. That is, in the first wave if you  recall there were people so critically ill, so many—a lot of them dying, a lot of them  surviving but in the hospital for sixty days, eighty days. One of our patients, her husband was  in the ICU for literally like two hundred days. When that happened, early in 2020, maybe 2021,  the mechanisms are obvious there. They often had sepsis. They often were on a ventilator  for a long period of time. They had hypoxic

injuries that were pretty straightforward. For the  patients with COVID who were never really sick, right, who developed long COVID, I'm  certainly not understanding with much precision what those mechanisms are. I  think it's a little bit mysterious still, and we need to obviously figure that out. Chin: Have you noticed a difference in how long COVID affects women versus men, or  different racial groups, or just different

backgrounds when it comes to older adults? Jackson: Yeah, certainly. We have found that our older patients are much more vulnerable  to cognitive insults than our younger ones are. I think that fits just generally with  what we know about cognitive reserve and the idea that our patients in the sixth or seventh  or maybe especially the eighth decade of life, they've got much diminished reserve, right?  They're a lot more vulnerable. We definitely

see some unique challenges in them. We do see  far more women than men who are attending our support groups, attending our clinics,  reporting cognitive challenges. I don't know if that's because there are any deficits  fundamentally or whether it's simply because, as a general rule, many of the women that  we see are somewhat more open to reporting symptoms than a lot of the men that we see. Chin: And have you seen any differences in

racial backgrounds across the U.S.? Jackson: We haven't seen a lot of differences in terms of symptom presentation  per se. I think in terms of treatment and in terms of access, we certainly have seen  some differences. You know, certainly in some minority communities where they might not be  as resource-rich as we would hope they would be, access is a challenge. Certainly in rural  America, access is a big challenge. I was on

a podcast not long ago in Michigan. It was about  rural healthcare, and we talked about the unique, particular and really widespread difficulties  people in rural America have finding a long COVID clinic. There are a hundred-and-some-odd  long COVID clinics in the United States, so that's fantastic, but there are some  predominantly rural states that don't have one at all and there are some large states where  there may be one and it's two hundred miles away.

This is a really big problem. Along with  a related problem, which is even pretty sophisticated healthcare consumers who have COVID,  they don't know what a neuropsychologist is, right? They don't understand the difference  between a neuropsychologist and a neurologist. They have no idea what a speech-language  pathologist is. So when we're making some

of these recommendations to them, gosh, they have  no idea where to turn. If we're not making them, unfortunately, nobody else very often is.  You know, help’s available, but people don't know how to pursue it, and that's a sad reality. Chin: One of the things you bring up in your book, and you mentioned it earlier in our conversation,  is this idea of rehab or cognitive rehabilitation. What exactly is that? Can you explain that for  our listeners, and then what's the difference

between the various forms that might be available? Jackson: Sure. It bothers me to no end, actually, that very often the only people that get cognitive  rehab are people who may have had a stroke, people who may have had an obvious traumatic  brain injury, when there are so many medical conditions that involve cognitive challenges,  which I think could get better with rehab—lupus,

multiple sclerosis. I could go down the list.  Typically, when I think of cognitive rehab, I think of a Barbara Wilson-driven, compensatory,  strategic-based approach, where someone is going to teach you some tools. They are going to give  you a way of thinking about taking on challenges you didn't have before. That could involve  reminders; it could involve the integration of

strategies; it could involve mindfulness and a lot  of things. It's not cognitive rehab positing that your brain is going to improve fundamentally—not  this approach—but your function hopefully will improve because you're engaging problems in  a different way. The method I’m a big fan of is called goal management training, validated  for the treatment of attention and executive

dysfunction. That's not the only approach. That  contrasts–compensatory, strategic-based approaches contrasts–with more neuroplasticity-based  approaches, and those, as you know, are pretty controversial. You've got true believers on  both sides. Some people who think brain games–that term is used very derisively–some people who think  brain games are a sham and a waste of time. Some people, of course, who think that they're the best  thing since sliced bread. The truth is probably in

the middle. When we engage people on computerized  video games, things of that sort, some of them—not all of them—anecdotally at least report that  those games help tremendously. So they're in our armamentarium. Do they work all the time? They  don’t. Do they help some people? They seem to. Thank you for actually breaking that  down and splitting the two, because whenever you hear cognitive rehab in general, in my  experience working with neuropsychologists,

there's always a little bit of a bristle. I'm  never sure what the response is going to be. Seeing the two different types and how one might  be more controversial than the other is helpful. Certainly being able to help people’s strategies  improve their function seems very worthwhile. In your book, you talk about the CONTACT trial. Is  that speaking to this idea of neuroplasticity,

or what exactly happened in this study? Jackson: We're in the process of analyzing the results, and I actually can't talk about  those before we've publicly discussed them. The CONTACT trial is explicitly based on a  neuroplasticity-friendly approach. There's a company called Akili, and they have designed a  video game, essentially. It's FDA-approved for

kids and teens with ADD and ADHD, and seems to  improve attention in that cohort. There's some evidence to support that, and so we're interested  in the proposition that it could impact cognition in adults. If you imagine that the symptoms  in long COVID are not that unlike ADD or ADHD,

I think it follows that treatments for ADD and  ADHD could be effective. I think that's why pharmacologically—and again, I’m not recommending  this, I’m just reporting—pharmacologically, there are neurologists and psychiatrists you'll  find around the country who do prescribe Adderall, who prescribe Ritalin, and in particular, the  one that is probably talked about the most

widely is guanfacine. There's a really nice case  series that was published by some folks at Yale, probably six or eight months ago, looking at  the effects of guanfacine on cognition in long COVID patients. Again, not a randomized trial,  a lot of limitations, but for many it seemed to be effective. I think the narrative here, Nate,  is just that in the cognitive realm, at least,

there are some things that seem to help. There's  an overarching long COVID narrative, which is, "We don't have any treatments, nothing we can  do," and that's a lot less hopeful than I want to be. In the cognitive arena, there are some  things that seem very helpful for some people, and that's good news in my mind. Chin: Well, I appreciate you. I understand you can't share any of your data, but  at least it's helpful for our listeners and for

me to know. I mean, this is the point of clinical  trials and the point of research—to explore these things that might help people. It takes time,  and unfortunately, I know people want things to happen right now, but it will take time. We look  forward to hearing the results of your study.

know, you take it, and you couldn't get COVID,  couldn't possibly get COVID. Sensible people, at the end of the day, fall prey to some of this  because they're so desperate, and I think that's why it's important to say you don't need to resort  to that. There are some actual methodologies—we've just described them—that for some people in the  cognitive arena really seem to help. I think it's important to note physical symptoms are a problem,  loss of taste and smell—those are a problem,

fatigue’s a problem. But many people  would rank-order cognitive functioning as the very highest, right? That domain where  impairment really is hard to deal with,that’s a domain where improvement is realistic. Chin: Speaking about the other ailments that people might experience—do you find that older  adults with long COVID tend to deal with other

medical issues that could be linked to thinking  change, mild cognitive impairment? Of course, I'm thinking about mental health  and thinking about those declines in attention or just the overall fatigue. Do  you see older adults responding differently? Yeah, I would say one thing that is  true of older adults that works in their favor, I think, is many of them are somewhat more  resilient by virtue of the hard life experiences

that they've had. I think what is especially  hard in the case of long COVID is we see people, often 25, 30, 40, 45, in the prime of life, no  comorbidities, no medical challenges, nothing. For them, it's really like they've just been hit  by a freight train, right? They have no context for anything. Many of our older patients—they've  already battled cancer and survived it; they've been in the ICU; perhaps they've had a heart  attack or two; maybe they've lost their spouse.

It isn't that that isn't sad, but it is that, in  some strange way, those losses have prepared them for the idea that, hey, life is really hard. I  think for some of our previously healthy people, COVID catches them off guard a lot more than  these folks who already have some skins on the wall with regard to medical problems. Chin: Well, I guess to end today, Jim, what’s the next steps in the field in  understanding long COVID and cognitive change?

Yeah, I think there are so many  next steps. From a systemic standpoint, I think one next step is we need to do a much  better job integrating neuropsychology into the care of medically ill patients. I think  neuropsychologists, in some ways, are uniquely qualified to operate at the intersection here of  cognitive and medical health, and I wish there were more of us to be involved here. There  needs to be more integration, so system-wide

that’s true for neuropsychology. It’s true for  speech and language pathology for sure. I think understanding the mechanisms, as we alluded, is  really important. I think the better we understand the mechanisms, obviously, the better we're going  to be able to develop treatments. I think figuring out how to scale cognitive rehab so that it is  available to large numbers of people—I think that's really important. I think trying to better  understand what the link is between mental health

and cognition in our patients is also important.  We certainly have seen some cases where people had pretty profound cognitive impairment after long  COVID; they also had depression and anxiety. As that depression and anxiety got treated, if you  will, then the cognition improved. So there's a lot to do, right? I love to smoke meat here in  Tennessee, and there's a saying: there's a lot of meat on the bone. And there is a lot of meat on  the bone when it comes to the work that we need to

do. If any of your listeners are interested in  kind of joining arms with me and with us here at Vanderbilt, I'd be delighted if they reached  out to me. If they want to buy a copy of my book and engage with me around it, nothing would  make me more happy. I'm really here to serve, so I hope I hear from some of your folks. Chin: Well, thank you, Jim. I appreciate having you on the Dementia Matters podcast.  You certainly—these next steps are a lot,

but they are needed, and I certainly hope we are  moving in that direction. But thank you again, and we hope to have you on in the future. Yeah, keep up the good work. Thank you.

outreach and production. Donate at the link in  the description. Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research  Center at the University of Wisconsin–Madison. It receives funding from private, university, state,  and national sources, including a grant from the National Institutes on Aging for Alzheimer's  Disease Research Centers. This episode of Dementia Matters was produced by Amy Lambright  Murphy and Caoilfhinn Rauwerdink and edited

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