[00:00:00] Christine Ko: Welcome back to SEE HEAR FEEL. Today is Part 2 with Dr. Todd Horowitz, who is an expert in attention. I will supply a brief bio here. Dr. Todd Horowitz has a PhD and is a prominent cognitive psychologist with expertise in how the mind processes visual information and the complexities of perception and attention. Today's episode will be focused on his research in attention and, specifically, cognitive impairments related to chemotherapy. He has made significant contributions to our understanding of visual memory, search, and attentional mechanisms, and is currently Program Director in the Behavioral Research Program in the Division of Cancer Control and Population Sciences at the National Cancer Institute.
[00:00:47] So we're going to jump right in.
[00:00:49] While I was on chemo and even after, and I don't know if this will make sense to you as an attention researcher. I would maybe call it related to attention. What I first noticed is I lost the ability to do more than one thing, at the same time. Supposedly no one can truly multitask, but I absolutely could not do it. Even literally driving and having music on, I didn't want to do it. I could maybe try to have the music on, ignore it, but it's just easier like, turn it off. I'm just going to drive. And it almost even became like walking? Yeah, just walk, no music. On a day to day basis, that was the thing that I noticed the most, that it felt like overload. People or these tasks are coming at me.... It was like, I cannot take it. I saw on your research biography that's something you study.
[00:01:34] Todd Horowitz: I think that's one of the most commonly reported symptoms now, along with forgetfulness, because of course we're used to multitasking. And we expect to be able to do it. And, that absolutely makes sense from an attention point of view. As you say, we don't actually multitask, right? You switch back and forth. If you imagine, switching back and forth more slowly, just trying to spread yourself across two different tasks, when you've got less capacity, it's going to be harder.
[00:01:58] Christine Ko: Yeah, what you just said is exactly what it feels like. My expectation of the pace of something was just not being met, like when we watch something in slow motion. It's slow motion and, if it fits in with the movie or whatever, it's fine, but I wouldn't want to watch a whole movie in slow motion. That would be really annoying. I feel like it makes sense because I was like, why does this bother me? So what's going on here? Can you talk about what chemo brain is?
[00:02:25] Todd Horowitz: You mentioned before we started recording, you said you think chemo brain is real. And I think that's really important to address because chemo brain is real. We have decades of research showing that to be the case. But it's not a hundred percent clear if the oncologists understand that. And I don't mean that in a condescending fashion. I mean that we have a lot of sort of educational work to do because anecdotally, I hear from patients, when I've occasionally published some high profile papers on this, and people write me saying, oh, thank you for writing about this because my oncologist said I was crazy.
[00:03:01] Okay, chemo brain.... First of all, we don't call it chemo brain anymore, for reasons I'll explain. The term chemo brain comes out of the experience of cancer patients who underwent chemotherapy and they have cognitive problems, that is problems with thinking and remembering and concentrating, that typically lasts beyond the end of chemotherapy. They can last for months or years. These are persistent effects. And so we don't call it chemo brain cause it's not just chemotherapy. You can observe these these problems with new targeted therapies, hormonal therapies, and so forth. It's not just chemotherapy. And it's not just therapy. If you compare patients before their treatment to say healthy controls, the patient's already performing not as well as the healthy controls. So that suggests that maybe the cancer might be doing something, or maybe the process of being diagnosed and becoming a cancer patient and all the accompanying stresses might be having some effect.
[00:04:01] So yeah, that's why we don't say chemo brain. In the research field, at least, we don't say chemo brain. My preferred term is cancer related cognitive impairments or CRCI . There are a couple of variations in that term floating around.
[00:04:12] Christine Ko: I like it. Okay, cancer related cognitive impairments. So are there ways to avoid or improve? cancer related cognitive impairments.
[00:04:22] Todd Horowitz: That's a very good question. The evidence for cancer related cognitive impairments became stronger over the last 20 years. There are various risk factors. The older you are, the more you're at risk. There are certain genetic markers that that leave people more at risk. There's the so called APOE gene; if you have certain alleles of that gene, the E4 allele, then you're more at risk. So one thing you can do is take into account people's risk factors before they get treatment. The oncologist can adjust the dosage of your therapy and what kind of therapy you're getting.
[00:04:58] People have been working on ideas for trying to block the part of the therapy that affects your brain. One of my grantees is testing out a drug in in marmosets that will block the effects of a particular chemotherapy regimen on the brain. People have been trying um, pharmacological treatments, of course, because, there's a lot of money to be made in pharmacological treatments. There's a bunch of potential physiological pathways we can intervene on while you're getting treatment to prevent you from getting chemo brain. And those studies, the evidence isn't very strong, so it's going to be a while before we see this in humans.
[00:05:37] The big thing right now is dealing with people who are already suffering from this, and what can we do for them? So far, what seems to be most effective are computerized cognitive training programs. And there's actually now a lot of evidence that just physical activity has strong effects and reliable effects and can really help people. Right now the best answer is cognitive training and and physical activity.
[00:06:02] Christine Ko: The cognitive training makes sense. The more you do something the better you get at it. Why do you think the physical exercise helps?
[00:06:08] Todd Horowitz: Physical exercise has a lot of benefits. I don't think we really know for sure what the pathways are in particular in CRCI. One thing it does is it just improves the cardiovascular system, and that's going to, in general, improve the blood flow to the brain. So you're just going to get all sorts of generalized benefits from that. I think that's probably the main pathway.
[00:06:30] Christine Ko: Not everyone gets cancer related cognitive impairments.
[00:06:34] Todd Horowitz: Yeah.
[00:06:34] Christine Ko: Do we know what percentage or it's really who knows?
[00:06:37] Todd Horowitz: Yeah, that's a really good question. It's very hard to measure that because unlike something like high blood pressure or whatever, there's no diagnostic criteria for cancer related cognitive impairments. Pretty much every time you study the phenomenon, you have to come up with your own definition. And so every study has slightly different definitions. There's a study from Val Schiller's group. It's about 18 years old now. But what they did was they had a sample of 90 breast cancer patients, and they tested their cognitive function in various ways. Depending on which rule you used, you could find that impairment was anywhere from 17 to 68%. So there's a lot of uncertainty about that. I think more recently people have started putting together some larger data sets. And it doesn't 100 percent solve the problem. But I feel pretty comfortable saying that about a third of people who are treated with chemotherapy are probably going to end up with some kind of noticeable kind of impairment that lasts at least six months to a year.
[00:07:48] Christine Ko: Oh, wow. Based on your research does this cancer related cognitive impairment or impairments have implications for attention or perception in general?
[00:07:58] Todd Horowitz: That's a really interesting question. Cancer related cognitive impairments, like most cognitive problems that people suffer from, have been studied almost exclusively using neuropsychological testing processes, for very good reasons. Neuropsychologists study clinical populations. They're involved in diagnosis. And we cognitive psychologists typically study people who don't have "deficits". We study people we think to be normal, which is to say, college students who enroll in psychology classes.
[00:08:31] Christine Ko: Who go to expensive universities.
[00:08:33] Todd Horowitz: Yes, typically an expensive university, highly representative population. Those two disciplines have very different populations. The approaches are very different. If you're in neuropsychology, you get the test, like the digit span test, and you don't change it. You use the same thing every time. Whereas if you're doing sort of basic cognitive psychology work, every experiment you do, you're changing something. You're coming up with a new design to get at a very specific question. And those two approaches have different pros and cons, but we use the same words. We use words like attention and concentration and working memory and executive function, but we don't always mean the same thing. When I just recently started working at NCI, and I was asked to present on a meta analysis about cancer related cognitive impairment. I was preparing my slides, and they break up the neuropsych tests into different domains like visual spatial processing and executive function and long term memory, short term memory. And the main finding in the paper was that the big problem that patients had was in visual spatial function. Which was interesting. But I looked at the other domains, one thing they found was that there wasn't any effect on attention, which I thought was a little weird for two reasons. One reason was people who have chemo brain complained a lot about attention. That's one of the big complaints. But also I was coming from a background as an attention researcher. And so I knew a lot about attention, so I was curious. All right. How are they measuring attention? And, they listed all the different neuropsych tests. I took a look at that list. I'm like, I don't think some of these have anything to do with attention at all. And so I went down a rabbit hole. And, pulled all of the papers from this meta analysis and then eventually from a whole bunch of other different meta analyses, again, working with my research fellow, Melissa Trevino, and wrote a paper where we said, there's this problem where people don't agree on which tests go in which box, right? In part because a lot of these neuropsych tests hit on multiple domains, but if you go from one meta analysis to another, this test might fall in attention in one and executive function in another, and this helps explain why they come to different conclusions. And so I remember in the paper we wrote a line something like, okay, this test probably measures attention, but there are other other tests like digit span that don't measure attention at all.
[00:11:00] And one of the reviewers, reviewer two, literally wrote back saying you can't say the digit span doesn't measure attention. This person was, a clinical neuropsychologist. And my first response was outrage. I am an attention expert. Of course I can say that it doesn't measure attention.
[00:11:17] And then I started to think about that. Like, well, What's the evidence? This led us to actually doing a big study where we tested about 600 participants on a big battery of tests, which included cognitive psychology paradigms that supposedly measure attention, and also like the top tests that neuropsychologists had used to measure attention in CRCI, to map those concepts and see, what are the relationships? We found that there was actually some agreement. Some neuropsych tests seemed to measure the capacity of attention. How many things can you attend to at once? So there were several tests that measured that. There were several tests that seem to measure your ability to shift attention and search.
[00:12:04] And then there were some neuropsych tests that didn't seem to match up to any of the the cognitive psych tests including digit span, which was its own little thing. So that gave me satisfaction. Some of the things that neuropsychologists call attention overlap with what cognitive psychologists call attention. And I think once we have that vocabulary, the learning goes both ways, right? I think it's going to be very useful to take what we know in cognitive psychology and develop maybe more sensitive and specific tests of people's neuropsychological function. And that's going to have implications, not just for CRCI, but in any condition where people are measuring cognition. Once we get that translation barrier down, we can start seeing what is it that affects attention? And what does that tell us about attention in general? But I think there's there's some work to do before we can get there.
[00:12:53] Christine Ko: Yeah, that's cool. Yeah. Do you have any final thoughts?
[00:12:58] Todd Horowitz: Yeah, this is another experience that has really brought home to me the importance of really translating across disciplines and working with people who have different complimentary knowledge basis to what you have and, really trying to understand what's going on rather than saying, I've been studying this topic for 20 years. I know this topic. I think that's like my takeaway as a scientist and as a program officer.
[00:13:24] I think I mentioned earlier, for the oncologist, the primary goal is to get rid of the cancer and to save the patient's life. And things that distract from that, they don't always want to focus on that, especially something like CRCI, which as I mentioned, we can't diagnose it. We can't give you a test and say, yes, you have CRCI, or, yes, you're going to get CRCI. So we've been actually doing a qualitative research project where we've been interviewing oncologists and oncology nurses and patients about their attitudes about CRCI. And, do they think it's real? What do they think? What do they think the research priorities should be? And things like that. What we find is that some oncologists will say, yeah, you can't see patients day in and day out and not notice that they're having these cognitive problems. This is a real thing. And some of the oncologists will say, yeah, okay, I know it's a real thing, but I don't think my colleagues do. So, I think there's an awareness issue there. And also, if we on our end can help develop better ways to detect and diagnose cancer related cognitive impairment and provide interventions like physical activity, or cognitive training, or give them a pill of some sort. Then that's really going to give the oncologist more motivation to take it seriously and to bring it up with their patients.
[00:14:38] Christine Ko: Yeah. Like even say, okay, you play this online game for five minutes a day and, you'll be less likely to have CRCI.
[00:14:48] Todd Horowitz: Exactly.
[00:14:49] Christine Ko: Yeah. That's awesome. I remember I had a 45 minute visit with a nurse before starting chemo, and I don't think she mentioned chemo brain or any cancer related cognitive impairment. She may have said that I could have some trouble with memory or attention, like maybe she used words like that, but I don't think so. I just don't think that anyone talked to me about cancer related cognitive impairment.... Definitely didn't use that term, so maybe as you said, it's just not a term used in medical circles.
[00:15:20] Todd Horowitz: Yeah, I think in part, they don't tell you about it because sometimes they're afraid that people won't want to go through the treatment if they're aware of this. And one of the quotes from one of our patients that we interviewed said , they give you all this information about your hair falling out. They can give you the same information that you're going to have reduced capacity. It's not in your head. You've got, you know, you've got reduced capacity.
[00:15:43] Christine Ko: I'm so glad that I was able to talk to you. I learned so much. Thank you.
[00:15:47] Todd Horowitz: Thank you.