Coping with Attention, Learning and Memory Challenges after Transplant

Many transplant survivors report difficulty with memory, attention and learning new things after transplant. Learn who is at risk, how long the problems typically persist and strategies to manage them.

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Coping with Attention, Learning and Memory Challenges after Transplant

Tuesday, May 3, 2022

Presenter: Michael Fediw MD, Medical Director of Cancer Rehabilitation, UT Southwestern Simmons Comprehensive Cancer Center.

Presentation is 37 minutes long with 19 minutes of Q & A.

Summary: The way we think and process information can change after transplant, at least in the short-term time. Called cognitive problems, paying attention, concentrating, remembering things and learning new skills can be difficult. This presentation discusses the factors that can cause cognitive problems and strategies to manage them.


  • Cognitive impairment can be caused by cancer itself, inflammation in the brain, other diseases, or medications. Certain types and higher dosages of chemotherapy increase the risk of cognitive impairment.  Apart from these factors, the aging process itself can also contribute to the problem.
  • The stress associated with having a transplant can impair cognitive functions like concentration. Problems with sleep, fatigue, depression, and anxiety can also contribute to cognitive impairment.
  • Exercise is one of the best “medicines” to improve stamina, relieve stress and reduce cognitive problems.

Key Points:

(02:01): Almost 50% of transplant recipients report cognitive impairments after transplant. Cognitive impairment can affect memory, concentration and how we organize our thoughts.

(06:38): Medical problems such as diabetes, heart failure, lung disease, kidney disease as well as aging can contribute to cognitive problems.

(09:16): Difficulty falling or staying asleep can affect your ability to think clearly after transplant.

 (11:37): Cognitive impairment is difficult to screen for and subjectively felt problems don’t always correlate with objective testing results.

(12:34): Doctors will initially test for medical problems such as thyroid problems, vitamin deficiencies or electrolyte imbalances that may cause cognitive problems.

(16:28): How people perceive their ability to think and process information after transplant, compared to the way they were able to do so before transplant, affects their quality of life.

(18:20): Twelve to eighteen months after transplant people will often notice improvement in their cognitive abilities.

(19:23): Cognitive behavioral therapy can help people better manage fatigue and stress that affect cognitive abilities.

(27:12): Cognitive behavioral therapy for sleep (CBT-I) is an excellent way to improve sleep, and your ability to process information.

(28:42): Non-drug therapies like mindfulness, relaxation, and meditation have been shown to improve mood and the ability to think clearly.

(32:58): For some patients, medication may help improve concentration or energy.

Transcript of Presentation:

(00:00): [Michala O'Brien] Introduction. Hello, my name is Michala O'Brien. Welcome to the workshop: Coping with Attention, Learning and Memory Challenges after Transplant. It is my pleasure to introduce you to Dr. Michael Fediw.

Dr. Fediw is a specialist in cancer rehabilitation at the UT Southwestern Medical Center in Dallas, Texas. He has experience in the treatment of pain, dysfunction, and cognitive impairment that can Inc occur after transplant. His goal is to help patients improve their cognitive function and to enhance their ability to perform daily activities and return to work. Please join me welcoming today, Dr. Fediw.

(00:47): [Dr. Michael Fediw] Overview of Talk. Thank you, Michala. I appreciate that intro. Hi, everyone. As Michala just mentioned, I'm Dr. Fediw. I'm a cancer rehabilitation specialist here in Dallas, and I'm happy to give you this talk today, and hopefully you guys can learn some things about really how we deal with the cognitive issues that occur after a stem cell transplant.

(01:04): So in order to start off, I'd like to mention that I just have nothing to disclose. I just get paid to be a doctor and treat patients, and that suits me just fine.

(01:15): I want to set the stage by saying first, a few things about just cancer survivorship. I know that not all individuals that get stem cell transplants are cancer survivors. However, the majority are, and that's what got me involved in this patient population.

The good news is, and the good problem to have, is that the cancer survival rates have been increasing steadily over the past many years and even decades. Unfortunately, this allows more opportunity for some of the long-term effects that sometimes cancer or stem cell transplant, itself, or just other treatments can have. And some of these side effects can lead to really poor function and low quality of life for patients.

(02:01): Nearly 50% of transplant recipients report cognitive impairments. It's been reported very commonly within the cancer population that cognitive impairment is a problem. It's in about as high as 60% of cancer patients in general, and as well as a 40% increase in just having a chance of having cognitive impairments later on in life. Of note, it's not on the slide, but stem cell transplants in particular report just as shy of 50% as well.

(02:27): Cognitive impairment can affect memory, concentration, how fast we process information and how we organize our thoughts. So what does this mean, ultimately? What is cognitive impairment? And ultimately what is cognition? What we describe as our cognition and cognitive abilities is really a collection of different domains and areas that control different functions and how we really create and organize our thoughts and process our thoughts and store and retrieve memories. Different examples of cognition include things like memory, your ability to organize your thoughts, your ability to pay attention or concentrate on different things, or just really with the speed with which you process different information.

(03:08): Objectively, there's a bunch of different cognitive domains that can be affected. And if you have impairment in any given one of these domains, then you can have cognitive impairment.

(03:20): Subjectively, really it's just a feeling of a person's decreased ability to think the way they're used to or perform cognitive functions or their normal roles compared to their own baseline that may or may not come up on testing. We'll talk about that later.

(03:38): Patient-reported chemo brain or chemo fog may not always show up on cognitive testing. So specifically after stem cell transplant, again, frequently reported. It's in just shy of about 50% like I mentioned earlier, that talk about some cognitive impairment. And a lot of patients describe it as subjective feelings of cognitive impairment that doesn't always correlate with, say a finding on a test or when we do cognitive testing and look at different domains of cognition. People sometimes still score normally compared to general populations, but they just feel a lot different. You'll hear different terms thrown out there described as chemo brain or chemo fog or transplant brain are things you might hear people talk about.

(04:19): Causes of cognitive impairment can include cancer itself, inflammation in the brain, chemotherapy, other diseases, or medications. So ultimately what causes this cognitive impairment, whether it's subjective or objective? This tends to be a little bit of a loaded question. There's been a lot of research done in this space and it's still not completely known that it's one specific thing. So there is evidence that shows that inflammation in the brain and the way your brain controls this inflammation can play a role. Also, just we know that having cancer itself has been associated with cognitive dysfunction, even before any kinds of treatments when you compare them to healthy controls.

(04:57): There are also other things that can play a role. Things like treatments like chemotherapy or other medical conditions that people have such as chronic lung disease or kidney dysfunction can also cause cognitive impairment. Sometimes medications we give people can have cognitive effects. Or there's other things that are external factors, which I'll get into in a little bit, but a lot of things that contribute to a person's ability to think the way they normally do.

(05:26): Interestingly enough, there's also research that shows just being aware that something could have a cognitive impact actually makes it more likely that people will experience that cognitive impact. So sometimes there's factors that we don't even fully understand, what we call psychosomatic factors, where people just, they think they might have something. So they're more likely to have it.

(05:48): Chemotherapy can affect cognitive function, with higher dosages increasing the risk of impairment. What we do know is, when I mentioned earlier, some of these other factors. So chemotherapy has been significantly associated with cognitive impairment. Different chemotherapies tend to have a higher likelihood... to have more of a direct effect on nerve tissue, but it also tends to be a dose-related effect. What I mean by that is... the higher the dosages of chemotherapeutic drugs you get, it tends to have a higher likelihood of having cognitive impairment, as well as the longer you're on some of these drugs tends to have a more significant effect. So despite the extent, the pattern, how long it lasts, there seems to be quite a bit of variability. And I think there's a lot of patient individuality and who experiences these kinds of symptoms.

(06:38): Diabetes, heart failure, lung disease, kidney disease as well as aging can contribute to cognitive impairment. So talking about the medical problems that can contribute. We know that things like diabetes and heart failure, lung disease, kidney disease, all of these things have been independently associated with changes in cognitive abilities. Also, they can cause secondary causes such as if medications are metabolized by, say, your liver and you're having liver dysfunction, then that might allow some of those medications to linger in your body a little bit longer, which raises the risk of side effects. Some of those being cognitive.

(07:12): Also just one thing that happens unfortunately, is as we age, it's the single most impactful, independent risk factor of cognitive changes. So we just don't tend to think the way we normally do as our bodies get older.

(07:29): The way chemotherapy affects your genes and DNA can affect cognitive abilities. There's also something called epigenetic factors. And I don't expect a lot of people here have heard of this, but essentially what these are, are factors that affect the way your genes and your DNA work. So they're reversible factors, and chemotherapy in particular has been shown to affect some of these factors that changes the way your DNA codes for things. And that can have an effect on people's cognition, as some of the molecules that are in your proteins that your DNA creates can also then affect some of that inflammation in the brain, for instance.

(08:04): The stress of transplant, itself, can have a significant affect your ability to think clearly, concentrate or remember things. Now, we're going to get into some of these external factors and I want to spend a little bit of extra time here, because I think this part is really, really important. I think that as it'll probably come as no surprise to majority of the people on this presentation, but just having either cancer or stem cell transplant can just come with a lot of stuff.

And part of that includes just stress. It's a very stressful thing to go through at times, particularly if you've had complications, or if you have to have a second transplant, or if you've had a prolonged hospitalization, or just the whole process itself, even if it goes smoothly, it can be a lot to deal with. And we know that having stress and psychological distress can really have a significant impact on your ability to think. And we see that in any patient population. Raising levels of stress on a body can make it more difficult for people to concentrate the way they normally do or remember things the way they normally do, because your brain is just spending so much of its time focusing on this one thing.

(09:16): Difficulty falling or staying asleep can affect your ability to think clearly after transplant. Sleep is another factor that's very important. It's pretty commonly described in my patients that sleep is affected after this process. So either they have difficulty falling asleep, or they tend to wake up more, or maybe there's other factors that come into play such as they're on a medication that makes them go to the bathroom a lot in the middle of the night or things. And that can also have a profound impact. I sometimes talk to my patients where I say if I took away all of your medical problems, but I just said for the next six months, you're going to sleep very poorly. You would probably see me at the end of those six months, you'd probably say, "I'm just not thinking the way I normally think." And it can have a pretty big impact on a person's day-to-day abilities. All of these have been independently associated with cognitive problems and especially cognitive problems after a stem cell transplant in particular.

 (10:15): Fatigue can affect memory and concentration. Another factor that comes into play is fatigue. I hear all the time, people can just say, "Doc, I'm just tired. I don't have the same energy level that I used to. It's just normal things that shouldn't poop me out, just tend to poop me out now." And there's been a lot of research done in this space. And several studies have showed that fatigue has also been shown to impact cognitive impairment and also just a greater subjective feeling. So patients that are tired also feel like they can't remember as much, or they can't find the words they want to say, or they can't concentrate the way they want to. A normal task that would be pretty easy for them is now more difficult.

(11:00): Unfortunately, it seems to be that this fatigue is more than you had a hard workout and you need to take a break. A lot of my patients, they say, "I lay down, I feel tired, I take a nap, but then when I get up, I don't feel well rested. I don't feel the same as I otherwise would if I had just done a strenuous activity." So there doesn't seem to be a way that you can nap this away.

(11:31): All of these factors contribute, but how do we actually diagnose it? How do we actually tell what is going on?

(11:37): Cognitive impairment is difficult to screen for and subjectively felt problems don’t always correlate with objective testing results. Unfortunately, we don't have great screens for this. There's not a questionnaire that I can give somebody that tells me exactly what's going on in their brain and exactly what's going on and how they think. There's been a lot of studies that look at people that report things like cognitive impairment after transplants. And then they do extensive batteries of cognitive testing on patients. And they don't seem to correlate always with the feeling of having cognitive impairment. So people may say, "Hey, I'm just not really thinking the way I normally do." But then when we do a test on that cognitive ability, it's in the normal ranges. It doesn't seem to be that people are going into early Alzheimer's, for instance, or that they're having significant dysfunction in a particular domain. Sometimes that is, and we'll get into that later.

(12:34): Doctors will test for medical problems such as thyroid problems, vitamin deficiencies or electrolyte imbalances that may cause cognitive problems. When you go see a doctor for these things, what are things you can expect them to do? Number one is they will examine you and rule out a lot of those other things that could be contributing. Like I said earlier, there's neurologic things that could be at play. There's organ dysfunction that can be at play like diabetes or liver dysfunction, for instance. And they can examine you to make sure that there's not obvious points of saying, "Okay, something else is going on that we need to treat," say cardiac dysfunction, for instance. They also will probably order some lab work. So blood work can look at other factors that could be contributing. They'll look at your kidney function for instance, or how your thyroid is functioning, because abnormal thyroid function is shown to be associated with cognitive impairment. They'll look at your electrolytes, which are things like your sodium levels. Low sodium can cause significant cognitive changes in people that can even lead to hospitalization. There's also vitamin deficiencies that have been shown to affect cognitive ability as well as nerve function. So some of the B vitamins are in that category.

(13:42): So there's a good chance that your doctor will, based on how you describe your symptoms and the way you present, will look at you and examine you, but also order a series of tests to make sure that there's no other dysfunction that could be treatable or reversible in that realm.

(13:57): Neuropsychological tests can help define how your brain is working. There's also something called neuropsychological testing. What this is, is extensive what we call batteries, which are just series of tests, more or less, which is like tests you might do on paper. And you go with a neuropsychologist for, it usually takes several hours. And they really have you do different tests that are specifically focusing on specific parts of the way your brain thinks. So they might look at memory, for instance, but what we describe as memory can actually be a fairly complex thing because from your brain, there's ways that your body stores memories and there's ways that your body creates memories. And then there's ways that your body retrieves those memories and all of those are different functions that can lead to a harder ability to remember.

(14:46): Other things could be there's memories that you create by seeing things, there's memories you create by hearing things or speaking things. And all of these can have different functions. And that's important because when it comes to treating it, sometimes you can actually utilize some of these other areas to actually restore the function that you wish even if one part is being affected.

(15:10): A brain scan may be used to determine the cause of cognitive changes that happen rapidly over a short period of time. So neuropsychological testing helps us do a deeper dive into someone's cognitive ability and see how their brain, overall, is functioning within each of these domains. And then if there's either specific findings on exams that would suggest there's something happening on the brain or something else that we can't rule out, then there's a good chance that they might get some brain imaging, particularly if it's a rapid change, something that's happened over a relatively short period of time. They might just get a scan of your brain to make sure there's not something else going on that's missing.

(15:49): When they have looked at brain scans after stem cell transplants, they have found some neurologic changes. They're not really specific. It's not like you have a new mass sitting there, but they have found changes that tend to affect certain parts of the brain, which coincidentally can be associated with cognitive issues, including the front of the brain and on the sides, what we call your temporal lobes as well. So, although there's usually not something to do that reverses that cause, they might look just to make sure there's not something else going on, or if there's evidence to point us in the direction of what could be causing your symptoms.

(16:28): How people perceive their ability to think and process information, compared to the way they were able to do so before transplant, affects their perceived quality of life. So ultimately how does this impact people? And I think this is probably the biggest duh slide, but it really can affect somebody's ability to function. And I think for a long time in medicine, I think we've ignored too much of this and how a person functions in their role is very important to them. When we've actually asked patients to fill out questionnaires about what is important to them, people's roles as workers, as family members, as citizens matters to them. Who you are is who you are, and you were that person for a very long time before you got whatever diagnosis caused you to have a stem cell transplant. And people want to try to return to that, or as close to that as possible, because that plays a lot into how they feel as a person. It can affect your ability to return to your role as a worker, or if you're in school age, being able to go back to school, get the profession that you want. It can cause increased levels of stress in your life.

(17:31): I have patients that for all objective purposes are doing great, but they're very distressed because they just don't think the way they used to and it really bothers them. I think we should take that very seriously. I think it's good to have a perspective if there are other things that are going well, but at the same time, we do want to take everything that you say seriously and do our very best to treat it and help it in any way that we can. And ultimately this leads to really a decreased quality of life, which is an individualized thing. Your quality of life is unique to you, and you should never have to apologize for that. And we should take that seriously because it affects your ability to be the person you are and the person you want to be.

(18:20): Twelve to eighteen months after transplant people tend to notice improvement in their cognitive abilities. Treatment. Some of it involves some reassurance, because what I'm getting at here is we don't have evidence that shows that people that have cognitive issues, it tends to be a progressive process where you just get worse and worse and worse and worse. For all we can tell, it doesn't really tend to get worse over time. And if anything, it tends to get better. The literature shows us that about one to one and a half years, about 12 to 18 months after transplant, people tend to notice an improvement in their cognitive abilities. Usually over the first one to six months, people start to report that they're having more issues thinking than normal, but then that tends to gradually improve some... Maybe not to their baseline level function, maybe so, but it usually shows some improvement, which is a good thing. So in also most cases, again, it doesn't lead to say an early onset of Alzheimer's or something as far as we can tell, or some other neurologic conditions such as multiple sclerosis.

(19:23): Cognitive behavioral therapy can help people better manage the fatigue and stress that affect cognitive abilities. We also want to clean up all of those other factors we talked about that could be contributing. Fatigue, for instance. There's something called cognitive behavioral therapy, which is basically a psychological treatment where it can include doing a lot of different things that look at addressing any unhelpful thoughts or behaviors that people might have that might be contributing.

For instance, people that just feel tired or feel like they won't be able to say the right thing, might find themselves becoming a little bit more reclusive. Or assuming they just can't do something because they've been having these issues. And it starts to address some of those catastrophizing behaviors, which ultimately don't help the situation, but can actually have a significant impact on hurting the situation. So helping people develop positive routines and managing their stress, those have shown to actually go a long way towards helping and fighting some of that fatigue. And doing things that we'll get into a little bit later, like exercise as an example of a positive routine that can have a profound effect on a person's ability to function as well as do a host of other things.

(20:39): Occupational therapists can help with fatigue and overall functional ability. Occupational therapists can also be helpful. For people that just have a really hard time, where they're so tired or they can't think to the point to where it's just affecting your ability to do your daily tasks or go to work, there's things you can do to help that. Where they'll help you find windows of your day that have higher function to maximize those windows or do things that aren't going to then wipe you out later. So you can pace yourself and get through your day better and really just improve your overall functional ability, whatever that may be.

(21:12): Exercise is a “magic drug” that is very helpful in restoring cognitive abilities. As I mentioned, exercise. If it was a pill, would be the magic drug. It really would. It has a profound amount of evidence that shows it's helpful with cognition, in particular, but it also helps with a lot of these other things. It helps with fatigue. It helps with sleep. It helps keep people strong. It helps with your cardiovascular system and your respiratory fitness. People that move more report higher quality of life, including in cancer patients, including in transplant patients.

All of this stuff has some of the best research behind it, of anything we have. It just doesn't come in a pill form. So it takes a little bit of effort, but people that move more tend to feel better, they tend to feel less tired. They tend to think better. I said, it's my cheesy phrase, but I always tell if exercise came in a pill form, it would be prescribed to every single person on the planet. Probably outside of the cancer population, but 100% within the cancer population and the transplant population. It really does that much for you.

(22:13): Exercise activity can start small and increase over time. I always counsel people, meet your body where it's at. The general recommendation from the American Academy of Cardiology or the American Cancer Society, for instance, usually recommends 150 minutes total in a week of moderate intensity exercise, which could include things like walking at a moderate pace. So that comes out to about 30 minutes, five days a week. So if you took a 30-minute walk, five days a week, that would suffice to meet the guideline. Some people they're just not there yet. They say, "I just feel so tired. It's so hard for me to do that." Or, "I have all these other things going on." I always tell people, start with what you can do, even if it's five minutes, 10 minutes. Go on a walk around your block, but make it intentional, start somewhere.

(23:03): People who exercise tend to think better, sleep better and see their mood improve. And you find, once you build a habit, it's much easier to build it into your routine. And I can tell you, time after time, people that tend to do that tend to start feeling better. So at minimum some way, but in a lot, most of the times in profound ways. And they start to feel better, they start to think better, their mood's better, they're sleeping better. So I can't stress the importance of exercise and moving more.

(23:26): And make it fun. If you don't like to walk, but you like to say, ride a bike or do Zumba or yoga. If you're in a wheelchair and you can't even stand up and do things, there's other ways you can incorporate exercise into your life even in that form. Things like hand bikes or chair yoga is a thing that can be very helpful. And there's also a meditative component to that, a wellness side that can also be helpful in this scenario.

(23:54): Treating sleep problems like sleep apnea and developing a consistent bedtime routine can cognition. And also treating sleep. Like I mentioned before, if I took every medical diagnosis away from you, and I took your transplant away from you, but I said you're going to sleep terribly, it would have effects. So we want to really optimize that. You might be referred to a sleep specialist to make sure you don't have something like sleep apnea, which has been shown to be associated with daytime tiredness and decreased levels of thinking. And that's basically where you're not breathing well enough and you're not getting enough oxygen into your body at night. And that obviously has a lot of effects but practicing good sleep hygiene can be really helpful with this.

(24:31): What we mean by good sleep hygiene, I believe you all are going to have a whole talk dedicated to sleep issues, but essentially it's making almost a ritual of your sleep and being really intentional about it. One thing that's hurt us in the modern world is screens. The light from a television or from a phone. And a lot of people, they either watch television before bed, or they look at their phone and scroll before bed. This actually tricks your brain into not understanding that it's time to go to bed. Before all modern society, our bodies worked on and they still work on what we call circadian rhythms, which is the majority of the world slept at night and was up during the day. And your body and your brain in particular works better when you do that. So this helps to optimize that.

(25:20): So going to bed at a consistent time, waking up at a consistent time, making sure that you're avoiding your bedroom, except when it's time to go to sleep. Those kinds of things help your brain when you get into your bed. Your brain understands it's time to go to bed, and it actually makes it a lot easier to fall asleep. So obviously avoiding things like caffeine before bed is just... I think everybody can understand that one pretty well.

 (25:44): Sleep medications may be appropriate for some people, but the benefits should be weighed against potential side effects. Sometimes medications are helpful. Some of those medications can involve very gentle, natural things like melatonin. And sometimes people need more actual sleep medications. So some tend to be better than others and have better research behind them. I like medications such as Trazodone, for instance. Some people utilize things like Benadryl or Ambien, are ones you might hear more commonly. I'm not as big a fan of those. If it really helps you, you can use them, but longer term, they tend not to have always the same effects. And sometimes they sedate people, but they don't give you good quality sleep and restful sleep, which can have an impact. And they also have a higher risk of side effects, which can become a problem later on. I counsel people to really have a conversation with your doctor about what types of medications, if they're needed, are most appropriate for you in your situation.

(26:44): Reducing stress can improve your ability to think clearly. Also, psychosocial factors. So talking about that stress piece. I can't tell you how many people have that. They can't think, they can't think, they can't think. And all of a sudden, they just change that stressful situation, or you allow them to cope with that stressful situation better, whether it's their diagnosis, whether it's their job, whether it's family issues and all of a sudden they're thinking better, it's a lot easier. They're remembering things better. So managing that is very important.

(27:12): Cognitive behavioral therapy for sleep (CBT-I) is an excellent way to improve sleep, and your ability to process information. There's what we mentioned earlier about cognitive behavioral therapy or CBT, also tends to help with this. It also tends to help with sleep and there's actually app-based programs, which can help you with all of these things. One of those would be the CBT-i Coach helps with insomnia. It's a free app that you can download. I don't have any financial relationship with any of these places. These are just things that my patients have found useful. There's something called 10% better, which has been helpful if you're having troubles with mood or coping.

(27:54): Dealing with depression and anxiety by talking with a therapist or through medication can help improve thinking. Depression and anxiety have an effect on your cognitive abilities. There's good evidence behind that and there's strong research behind that. And if you treat that, whether it's through natural causes like coping or individual therapy, talking to a psychologist about it, or by even medication choices, things like antidepressants can sometimes be necessary. People tend to think better when they're not depressed, when they're not very anxious. There's a very strong evidence base for that. Because again, once you think, "Oh my goodness, I'm not going to be able to think. I'm not going to be able to remember" that causes stress, which causes anxiety that actually makes it harder to think and harder to remember. So you got to work your way backwards a little bit to really tackle those things and really approach it from different angles.

(28:42): Non-drug therapies like mindfulness, relaxation, and meditation have been shown to improve mood and the ability to think clearly. Like I said, I'm not the type of physician that really pushes a ton of medication on people if I can help it, but sometimes it's just necessary. Sometimes it's really important. Sometimes the whole process just becomes overwhelming for people and they really just can't concentrate on anything else. And that has a big impact on them. So even things like mindfulness, relaxation, even meditation. I mean, I think if you look at a lot of organizations like Livestrong and a lot of cancer centers will have access to things like tai chi or things, because it's shown to be helpful. Patients that do those things tend to feel better. They tend to think better.

(29:17): Cognitive rehabilitation and brain training can improve cognitive functioning. And then there's a rehabilitative piece. So cognitive rehabilitation can improve brain function and there's different ways it can do that. There are certain things, what I call brain training. So some of this can be games or app-based things that make you use your brain. And the more you use it, it's like a muscle. It gets stronger, it works a little bit better. And there's also app-based things like Lumosity that tend to help with these specific brain training games.

(29:47): Speech pathologists can also help retrain the brain. You can also work with a speech therapist. Speech therapists are actually called speech language pathologists. So they have the word speech in their names, but they do more than just work on speaking. So people get confused when they say, "Why do you want me to see a speech therapist? I speak fine." It's because they work on cognition. So they're the therapist that own cognition and cognitive abilities. And they may not go into as extensive testing as say the neuropsychological testing is, but for some people that's actually much preferred because it's just really hard to make, going to think for three hours. But they can also look at different domains of cognition and really see which ones might be affected and really focus on that. Okay, here's some exercises or some brain games that'll focus on say, your concentration ability, or will focus on your verbal memory or your visuals spatial abilities, which is your ability to connect what your eyes are seeing to what your hands are doing. So they can be really, really helpful. And that's focusing on those pieces of your brain that might not be functioning as well, particularly if something comes up on the testing.

(30:53): Adaptive strategies, like writing things down or using electronic devices to keep track of schedules can be helpful. But then, there's also what we call the adaptive piece. In the rehab world, there's almost always two realms we can go. There's the restorative piece where say you have a weak muscle and we want to get that muscle strong. We try to restore the function of that muscle to what it was able to do before. Or there's adaptive strategies. For instance, heaven forbid, somebody gets to a terrible car accident, has a spinal cord injury and loses the ability to use their legs. And we know that they won't regain enough strength and be able to walk again. You can still use adaptive strategies to change the outcome of how that person is able to be independent by say, using wheelchairs or using a board that can get them in and out of a bed to a chair, a chair to a car, and then modifying their car to allow them to drive. These are more of the adaptive strategies. And from a cognitive standpoint, there's a lot of adaptations you can do that can help with really your ability to function.

(31:49): A good example is if your auditory memory, which is the memories you make by hearing things is poor. So when somebody tells you something, it's hard to remember that, but your visual memory is intact. Writing things down also gives now your brain another backdoor to create that memory or creating memory books or logbooks or setting yourself reminders. One of the nice things about having smartphones now is there's a lot of things that they do to help you in this realm where you can set alarms that remind you to do things. And you can just set up a schedule that way or have a family member help you.

(32:23): Minimizing distractions can improve your ability to think clearly. They can also talk about when you're doing certain tests, minimize and adjust your environment to optimize that. So minimize the number of distractions that you might be experiencing. This can also be really helpful, particularly in work settings, or if there's just a task you really need to get done. So speech therapists can be really helpful and your physician can also help guide you in ways to do those kinds of things, to really change the ultimate outcome, which is the functional piece, which is going back to what we talked about earlier, getting you back to your role, getting you back to the person you want to be and being able to do the things you want to do.

(32:58): For some patients, medications like Ritalin, may help improve concentration.  And then last, the thing I want to talk about is sometimes medications are helpful. I usually don't jump to these right off the bat, depending on how the patient presents, because if we can do it without it, then we can do it without it. We'd risk, no side effects and those kinds of things. But there are ones that can be helpful and particularly things that we call neurostimulants, which help increase your energy or your ability to concentrate in that realm. There are ones that have been studied specifically in patients that have cancer-related cognitive impairment.

(33:38): One of those is methylphenidate. You might have heard this by the brand-named Ritalin. They give it to a lot of times children that have ADHD, but for people that have concentration issues, which tends to be focus coming from the front of the brain. So if you have frontal lobe dysfunction and you really have a hard time concentrating, where you feel you can't remember things, but you really just can't pay enough attention on one thing to really create a memory, this can help your brain focus more and stay on task enough to get through some of those memories and reason through things a little bit better.

(34:11): Other medications give people more energy or help prevent cognitive problems from progressing, which may be helpful. Modafinil is a medication that helps give people more energy. So if people have a significant fatigue component, Modafinil can be helpful. And then donepezil is an Alzheimer's drug that helps people from progressing in their cognitive abilities, in the wrong direction. It helps prevent people from going further. And when they've looked at certain patients in the cancer world, there's been some mild evidence to show that it can be helpful in certain populations about people's ability to think through problems and reason and helps with your processing speed a little bit.

(34:56): Each case is different so consulting with your doctor about treatment is important. So all of these have some small studies that show some benefit. We don't have mountains of research, and I really think more research needs to be done in this space in particular, but what's been out there has shown some promise in this realm. In some cases it might be a very reasonable option to talk to your doctor about if any of these things would be useful for you or be worth trialing. And overall they're generally pretty well tolerated, which is also nice. But all that comes to an individual standpoint, which is really just weighing risk and benefits, hoping to help the problem you're presenting with while also not creating any harm.

Dr. Michael Fediw (35:38): Cognitive impairment after a stem cell transplant is a complicated process and can be caused by a number of factors. In summary, cognitive impairment after stem cell transplant is a pretty complicated process. There are neurologic things that could be going on. There are inflammatory things that could be going on, and there could be a whole host of other things going on that could all be having, at minimum, a contribution or if not, causing the entire problem. So the best treatment really looks at all of these different things to try to optimize everything, particularly areas that are presenting as clearly deficient or dysfunctional.

And in most cases, the cognitive impairments shouldn't get worse. And if anything, it can improve over time, which is also reassuring, even if we do nothing. So sometimes the best answer is just give this a little bit of time and we'll see if things just improve on their own, but there's physicians out there that can be helpful.

(36:34): A cancer rehab physician often has expertise in managing cognitive problems after transplant. If you can get in touch with a cancer rehab physician, a lot of times they have expertise in this, but sometimes other rehab physicians or sometimes neurologists or different people own these things. It's a little bit state and institution specific. So the best thing to do is ask your doctors, ask your oncologist, "Hey, does anybody help with people that are having trouble thinking?" Hopefully they would know, and they may refer you to somebody that can really help you.

(37:02): With that being said, that's the end of my slides. I have some resources and reference here if anybody wants to read some of these studies that I use, themselves, but otherwise I would love to take some questions.

(37:16): [Michala O'Brien]            Q & A. Thank you Dr. Fediw for this excellent presentation. We will now take questions. All right, our first question is: "What cognitive therapies do you find helpful after transplant? Have you ever heard of the Feuerstein method? It'll be two years after my transplant this July and my cognitive function has declined."

(37:46): [Dr. Michael Fediw] Thank you for that question. Yeah, there's different specific therapies that can be helpful. Feuerstein is one of them. Usually it's a little bit dependent on what therapists you're working with and who it is. For instance, psychologists and neuropsychologists might use things a little bit differently than say a speech therapist or an occupational therapist, but there's a variety of some. And some of it also just depends on how you're presenting or what seems to be the issue. Is it more of a concentration issue? Is it more of a memory issue? But usually either your physician or your speech therapist or your psychologist, particularly the neuropsychologist can help you decide which one is the best for you.

(38:40): [Michala O'Brien] Okay. Thank you. The next question is: "I have trouble with focus and it feels like I never finish a task. What can I do to get my focus back?"

(38:50): [Dr. Michael Fediw] Great question. I hear that kind of thing all the time. It's a little bit tricky based on how I went through the presentation. You see, there's a lot of things that can play into that, but some of that could be actual concentration or some of that could be executive function tasks. Executive functioning tasks look at how your brain can reason and can connect dots and plan and execute given tasks. So depending on what's being more affected, I would say first things is do the things that you can manage yourself. Look at your sleep, try to get better there, start exercising, start moving your body more. Try to modify your environment in ways that will help you and break big tasks into little tasks and make them into really bite size, small pieces that you can then do one thing at a time and maybe write down a timeline for yourself.

(39:48): Otherwise, for most people that's usually the kind of thing that's helpful to work with like a speech therapist on, as well as obviously modifying the rest of your risk factors. But yeah, cognitive behavior therapy can also be helpful. Some of those apps I mentioned or doing it with a licensed psychologist can be helpful.

(40:06): [Michala O'Brien] Thank you. This question is from a fellow Texan. They had their transplant over 10 years ago and they noticed difficulty with recall and concentration. "For the first time, I actually had to work hard to maintain my grades, my handwriting, and I also had some improvement, but not back to pre-transplant. And it's upsetting." They're wondering what your thoughts are about the effectiveness of over-the-counter memory supplements.

(40:39): [Dr. Michael Fediw] In this scenario, it's hard for me to make a formal recommendation without knowing the specifics of this person. For instance, some of it is what is their age and some of their other risk factors. I don't think that taking over-the-counter supplementation will harm you. However, a lot of those types of supplements don't have good research behind their actual effectiveness. So I would take all that with a grain of salt and it would probably be more useful to either see somebody formally for that, or talk to your doctor a little bit about, like say your oncologist or whoever's managing your transplant, about things. Because some of those supplements also can interact with some of your other medications. So you do have to be a little bit careful about what you're trying. So I don't typically strongly recommend any of the over-the-counter things, but some people try them and find them beneficial. So if they're not harmful and they don't interact with other things, I'm usually pretty okay with people trying some of the things, but we don't have good evidence that show any particular one's work.

(41:49): [Michala O'Brien] Thank you. "How do you differentiate between long-term chemo brain and warning signs of dementia or early onset of Alzheimer's? I'm 77 years old and 29 years post autologous transplant."

(42:05): [Dr. Michael Fediw] Sure. Another great question. Unfortunately as you know and I mentioned earlier, age is a risk factor for cognitive issues. Some of it is the chronicity of it. So one of those things is, Alzheimer's is a progressive problem. It tends to get worse over time. Well, chemo brain and fog and transplant brain and those things don't. If anything, they could just plateau or improve some. That's one way. There are also other hallmark things I look for. Without getting too much into the details, for instance, people that have Alzheimer's, they start to do things that people with chemo brain don't typically do. People with chemo brain just have a hard time thinking, they might get a little lost in the conversation. They might have some of those executive functioning issues where it's hard to say, follow a task.

(42:53): People with Alzheimer's or, for instance, or other degenerative neurocognitive disorders, it tends to be a little bit more severe. For instance, they can't even watch television shows because they just get completely lost or they get lost going home in the house they've lived in for 20 years, those things. So it tends to be a little bit more apparent into where it's not just, "Hey, I can't do normal things in my roles," but it's actually like, "I'm getting completely lost doing things I've done for decades." And because Alzheimer's tend to be more of a short-term memory problem, usually the long-term memory stuff should be more intact. When that stuff starts to become affected, then that's a little bit more concerning for something a little bit more serious or something actually happening more in the brain tissue going on.

(43:41): [Michala O'Brien] Thank you. Is an increase in melancholy or depression common in post-transplant patients?

(43:49): [Dr. Michael Fediw] Yeah, I would say so. I don't know the statistics on it, but just in my experience, yeah, for sure. And it's important to address those things. It's not shameful to say that. Everybody that's had this process, whether it's easy or hard, has gone through a lot and there's no shame in saying that and that can be very taxing mentally. What I find is the mental side tends to affect the physical side and affect the cognitive side. So don't ignore it.

(44:23): [Michala O'Brien] Next question, are there any programs to help BMT survivors to connect with remote work if they're unable to return to their previous jobs? Is there evidence that getting back to work either part-time or full-time would improve cognitive impairment or prevent it?

(44:43): [Dr. Michael Fediw] I don't know of any research that says specifically that returning to work makes people think better. Unless returning to work... And again, there's not research behind this, but hypothetically returning to work makes people just feel better in their role and that treats their mood and their stress. And then that makes them think better. But just going back to work itself and challenging your brain that way, while hypothetically it might help, I don't think there's any actual research done in that space. I'm sorry, what was the first part of the question?

(45:19): [Michala O'Brien] Let's see. It says are there any programs to help BMT survivors connect with remote work if they're unable to return to their previous jobs?

(45:28): [Dr. Michael Fediw] Not that I'm aware of. That's an excellent question. I wish I had a better answer for that. I don't know. There should be, because I think that would be excellent, especially with nowadays. I think one of the "silver linings" to this whole pandemic is I think it's made it pretty apparent that a lot of people can work from home and work remotely, which helps a lot of people, particularly people that are immunocompromised and scared to go into a public work setting. But there's no rehab programs that I'm aware of that will connect you to those things. I would think if there were touching base with either organizations like the American Cancer Society or Livestrong, I would think would have maybe some resources there, but not that I'm specifically aware of.

(46:15): [Michala O'Brien] Okay, thank you. How does inflammation create or add to brain function?

(46:22): [Dr. Michael Fediw] That's a complicated question. That's a very complicated question. I'll try to answer it as simply as I can, but that's a whole talk in and of itself. But basically there's different processes in your bodies and there's positive sides and negative sides. And negative isn't always a bad thing. What I mean by negative sides is there's more stimulative and depressive functions. And these are regulated by the neurons, which are the nerves and the nerve cells in your brain, but there's a lot of things. There's also inflammatory processes, which help protect your brain, but can also cause issues. And also there's the metabolism of your brain, which is how your brain uses energy that is actually pretty complicated. And it's tied to some of these inflammatory processes. We call it dysregulation. So some of those inflammatory molecules will then cause other things that affect the way your brain utilizes energy appropriately and creates additional molecules that cause extra stress, something called reactive oxygen species and things like that.

(47:40): So that's a very complicated question, probably more than I could just answer here, but it can certainly have an effect. And it's usually what we call cytokine dysregulation, which cytokines are inflammatory proteins throughout your whole body, but especially in the neurologic system.

(47:58): [Michala O'Brien] Okay. The next question, what are the benefits of mindfulness in assisting with memory and recall?

(48:08): [Dr. Michael Fediw] Good. Really it helps with some of those external factors I think. Is it really helps people relax yourself, get into a better shape that you're able to... you're optimizing your environment to either learn or to function. And it also helps again, some of those, "Oh my goodness, I don't want to do this because I can't do it or because I'm not going to be able to do it," which you don't know if you don't try, but also increasing that stress makes it harder because you're thinking... It's almost like the people that when they're trying to go to sleep and all they think about is not being able to sleep, so that prevents them from going to sleep. It's that thing. So mindfulness puts you in just a calm restful state that then optimizes you for your ability to think and reason and function.

(48:57): [Michala O'Brien] There's a pharmaceutical question. Have you ever recommended nortriptyline as a sleep aid? Nortriptyline?

(49:04): [Dr. Michael Fediw] Generally, no. I use nortriptyline quite a bit, but usually more for nerve pain. The reason I don't like it as a sleep aid, although it can be helpful, I would recommend it as a sleep aid for patients that might have headaches, for instance. It can be good for that or like I said, nerve pain. But otherwise, there's other sleep medications that have a better sleep profile. Nortriptyline tends to cause what's called anticholinergic effects, which in most people aren't too bad unless you take too high of a dose. But particularly in older patients can cause like blood pressure drops and things like that and even cognitive issues. Things you wouldn't want. So it's not a go-to for me for sleep, but it is a good medication in other indications.

(49:56): [Michala O'Brien] This question, is there any research that shows that learning a new language or art therapy or music can assist in preventing cognitive impairments?

(50:09): [Dr. Michael Fediw] Not that I'm aware of specifically, but if you're a musician or say a linguist or something that you enjoy that, and then adding that into say like a rehab program. I would be a fan of that, but I don't think there's specific research that I'm aware about there that looks at that specifically as a rehab program.

(50:27): [Michala O'Brien] Here's a couple questions on supplements. I know you mentioned that a little bit earlier. What do you think about taking DHA oil supplements coming from either an algae source or a fish source? And then what about MCT oil? I think that's the coconut oil.

(50:49): [Dr. Michael Fediw] Again, there's different ones that they claim that they help some of these functions and they use different amino acids. I think the MCT uses amino acids of different sizes to try to improve memory and cognition. I don't think the evidence base is super strong for them. I can tell you, I really like an app called... I just blanked on the name of it. It's called About Herbs. It's an app that was created by Memorial Sloan Kettering, the cancer hospital in New York City. And it's very good for supplements. What it does is it's a database that you can search different supplements and look at what they say they're helpful for and what the actual research is behind them, as well as potential side effects, interactions. I actually use this app quite a bit because there's a million supplements out there and it's sometimes hard to keep up with them. But I personally like this one in particular and it's called About Herbs. And they have a physician side and then they also have a more of a patient-focused side. Otherwise, I like that one.

(52:15): Again, those other things, while they typically don't tend to be harmful, the evidence isn't strong that they're going to make a big difference. But I always say if you want to try it, usually with supplements you got to be on them for a little bit. So usually I'll give people like three months on something like that and say, "If you really want to try it, let's try it for three months." If you feel better in that timeframe, we'll stay on it. And if not, we'll just stop it.

(52:42): [Michala O'Brien] Okay. This question is, is there a way to diagnose the difference between issues that are chemotherapy related versus just the normal aging process in memory or recall issues? How could I tell?

(52:58): [Dr. Michael Fediw] The easiest way to tell is timing. Were you one way and all of a sudden you started taking chemo, now you're another way? And then as you took more of that chemo, it progressed. And then if you came off that chemo, did it improve or get better? That's usually the easiest way to tell. From a neurologic standpoint, most of the neurotoxicity that happens from chemo doesn't continue to progress after you've stopped the chemotherapeutic agent. So it should either usually improve and then either recover or improve and plateau.

(53:32): I know that from the peripheral nerve injury. So neuropathy that happens after chemotherapies shouldn't, "Hey, I took a cisplatin agent or something like that and I got neuropathy and then I was fine. It went away. And then four years later, also I have neuropathy and it's from the chemo." That's not from the chemo. Same with the cognitive impairment. It shouldn't just all of a sudden go away and then all of a sudden, suddenly get worse later on. It's usually a dose-related effect. So the more you get, the longer you're on it, it should have just a steady progression, if that makes sense.

(54:07): [Michala O'Brien] Okay. This looks like we're coming up to one of our last questions. It's an exercise question. It says, "My doctor suggested I exercise for 30 minutes a day. Would it be okay if I split up that 30 minutes into three sessions of 10 minute exercising?"

(54:24): [Dr. Michael Fediw] Absolutely. Great way to do it. If you have a hard time finding 30 minutes of your day, or if it's just too much for your body to handle, split it up. That is perfectly fine and it still counts. The typical cheeky phrase I give people is if you can't do 30 minutes, don't make the alternative nothing. Do something. And if you have to split it up, split it up. That's a perfectly fine way to do it and the cumulative benefit is still helpful. And that works with a lot of things. Even on a personal note, I had lost some weight and I did a similar thing where I kept telling myself, I didn't have time in my day. So I made it so simple that I couldn't not find time. I made it five minutes or 10 minutes. And then that way, the only thing stopped me from doing it was then just me. Once I took that part out, I built a good habit and was able to be very successful in that.

(55:18): So same way in this case, even if you can start, start with what your body can handle. Try to break it up into five or 10 minute sessions. And then even if you can only do one or two of those, build up. You'll find that within a relatively short timeframe, you should be able to work your way up pretty quickly. But a lot of it is more of the habit than anything else.

(55:39): [Michala O'Brien] Closing. Well, great. I wanted to say on behalf of BMT InfoNet and our partners, I want to thank you Dr. Fediw for your helpful remarks. And thank you, the audience, for your excellent questions. Enjoy the rest of the symposium today.


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