Coping with Attention, Learning and Memory Problems after Transplant

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Coping with Attention, Learning and Memory Problems after Transplant

Saturday, April 17, 2021

Presenter: Shelli Kesler PhD, Associate Professor, Co-Chair of Survivorship and Supportive Care Research, Livestrong Cancer Institute, The University of Texas at Austin

Presentation is 35 minutes long with 23 minutes of Q & A.

Summary:  Many patients experience cognitive problems after a bone marrow, stem cell or cord blood transplant. Cognitive problems include changes in the way a person receives, processes and retains information, and organizational skills. The problems may be temporary or long-term. There are interventions that can help patients improve cognitive functioning after transplant. This presentation describes the causes and symptoms of cognitive impairments and appropriate remedies.

Highlights:

• About 40% of transplant patients will have long-term cognitive impairment. The good news is that the brain is a plastic organ that can create new brain cells.
• Evidence from research on brain functioning and cognitive impairment has identified four types of interventions that can improve cognitive functioning after transplant.
• Physical exercise and mental stimulation are the best “medicine” for cognitive health especially when these activities are done on a regular, scheduled basis.

Key Points:

(02:51) “Chemo brain” is not an accurate term because cognitive problems can arise from many other aspects of treatment like the underlying disease, irradiation, or medications.

(05:11) Some risk factors for cognitive problems are non-modifiable due to genetics, disease severity, or treatment intensity.

(06:44) Other risk factors can be modified by reducing stress, improving sleep, and becoming more active.

(07:32) Chronic illness, chemotherapy and radiation cause inflammation that can be toxic to the brain.

(08:50) Brain MRI scans can reveal lower brain volumes and reduced gray matter after transplant.

(11:06) Cognitive functioning can be assessed with neuropsychological measures, although these tests have limitations that also need to be recognized.

(15:28) Physical activity is by far the most important remedy for cognitive impairments and can improve heart health and many functional capacities.

(19:53) Computerized cognitive training programs are helpful for some patients, as is “active journaling” which engages multiple cognitive skills.

(27:02) Cognitive rehab is a more formal, in-clinic program provided by occupational therapists or other specialists. It can teach compensatory strategies for cognitive challenges while the brain recovers.

(30:43) There are medications and supplements for cognitive impairment that help some people but they have side effects and clinical trials show mixed results.

Transcript of Presentation:

(00:01) [Sue Stewart]        Introduction. Welcome, everyone. This is the workshop, Coping with Attention, Learning, and Memory Problems after Transplant. My name is Sue Stewart. I will be your moderator today.

(00:14) I'd like to introduce you to Dr. Shelli Kesler, who will be our speaker. Dr.  Kesler is an Associate Professor of Nursing and Diagnostic Medicine and Oncology at the University of Texas at Austin. She's also the Co-Chair of Survivorship and Supportive Peer Research for the Livestrong Cancer Institute.  Dr. Kesler's research focuses on the cognitive effects of cancer treatments using neuroimaging and machine learning methods to diagnose and predict cognitive problems in patients with breast, brain, and blood cancers. Please join me in welcoming Dr. Kesler.

(00:56) [Shelli Kesler]      Overview of talk. Hello, everyone. Thank you for joining me today to talk about attention learning and memory problems after transplant. These problems are very common after transplant as well as treatments for cancer. They are referred to as cancer-related cognitive impairment. I'm going to tell you more about what this means. I'll also talk about who tends to be affected, how long these problems can last, what we know currently about the underlying causes of cognitive impairment, how we measure or evaluate these problems, and importantly, what can be done about them.

(01:39) Cognition involves a variety of important skills. First of all, cognition refers to the skills that your brain is responsible for. These skills include problem solving, reasoning, and logic, learning new things, and being able to remember those things later on, focusing and paying attention, and the ability to speak and understand what others are saying to you. There are, of course, many other cognitive skills besides these. This gives you an idea of what I mean. I know that transplant doesn't happen only for patients with cancer. What we currently know regarding transplant related cognitive issues comes from this field. That's what I will be focusing on today.

(02:24) Cognitive problems can occur before, during, and/or after transplant, and other related treatment. Problem solving, attention, memory, how fast you think, and how quickly you can find words that you want to say are the most commonly affected cognitive skills. Everyone is different and can have problems in areas that other individuals do not.

(02:51) “Chemo brain” is not an accurate term because cognitive problems have other causes as well. You may have heard of cognitive problems in patients with cancer being referred to as chemo brain. This is not a very accurate term, because we know that cognitive problems are associated with many different types of treatment, including transplant, immunotherapies, high dose steroids, radiation, and the cancer or disease itself. It's really difficult to determine which one of these is the actual culprit, because, as you know, they tend to occur together. It's really hard, actually, to assess cognitive function before and after each one of these treatments to try to figure that out.

(03:35) About 40% of transplant patients will have long-term cognitive impairment. The number of people who have cognitive problems after transplant depends on the disease in question, how far out from transplant cognitive function is evaluated, and what measures are used to evaluate it. There isn't just one answer in the research literature, but we try to focus on patients who have cognitive problems chronically, because they are the ones who will probably need the most assistance. With that in mind, based on the current research, about 40%, or two out of every five patients will have long-term cognitive impairment after transplant.

(04:19) Cognitive problems differ in their timing and trajectory for different patients. Some patients have cognitive problems lasting months or years. Some patients seem to have permanent difficulties that haven't shown any recovery or improvement even decades later. Some don't have any difficulties after transplant, but then develop some problems later on. Some have problems right away that get worse over time. Let's remember that most patients, actually, don't ever have problems, the other three out of every five patients who don't have significant cognitive impairment.

( 04:53) The course or trajectory of cognitive problems can look very different for each person. One person's experience with cognitive problems might be quite different from another person, even though they might have had the same disease and the same treatments.

(05:11) Some risk factors for cognitive problems are non-modifiable due to genetics, disease severity, or treatment intensity. The difference in the course of cognitive problems is often influenced by certain risk factors. There are risk factors that are non-modifiable, meaning that we're just stuck with them and we can't really do much about them. These include older age and certain genetic risk factors. Now, these are not genetic abnormalities, but just normal variations in our DNA that give us certain advantages or disadvantages.

(05:43) For example, because of my genetics, I'm only five foot three inches tall. This is not an abnormality per se, I guess, depending on who you ask. It does disadvantage me for certain things like reaching items that are on a high shelf or playing basketball. There are genetic variations like this that can cause disadvantages for cognitive function that can become magnified when you have a disease or an injury.

(06:15) Another non-modifiable risk factor is higher disease severity. Patients with standard or high risk disease tend to have more cognitive problems than patients with low risk disease, for example.

(06:30) Related to this is treatment intensity. Patients with higher disease severity often receive more intensive treatments. These are associated with a higher risk for cognitive problems.

(06:44) Other risk factors can be modified such as stress, sleep, and mental and/or physical activity. Fortunately, there are a lot of factors that can be modified or changed. Chronic stress is one of these. Stress is very toxic to brain cells. Managing stress level is very important for brain health.

(06:59) Sleep is also really critical for brain functions, including memory and learning. Plus, when you're fatigued from not having enough sleep, it's really difficult for your brain to work properly.

(07:13) Research evidence has shown us that patients with low mental and/or low physical activity are at the highest risk for cognitive problems. It's very important to exercise both the brain and the body. I'll talk more about how to do that later on.

(07:32) Chronic illness, chemotherapy and radiation cause inflammation that can be toxic to the brain. There are several disease and treatment related processes that are believed to result in cognitive impairment after transplant. Chronic illness is associated with elevated inflammation, and that inflammation can be very toxic to the brain.

(07:50) Treatment such as chemotherapy and radiation also cause elevated inflammation. These treatments can additionally cause DNA and mitochondrial damage. Mitochondria are molecules inside our cells that are responsible for energy production. The brain is the largest consumer of energy in the body. You can imagine if our mitochondria are affected, that our brain would be one of the most vulnerable organs to that disruption.

(08:22) Many treatments create neurotoxicity resulting in cognitive impairment. Now, the cells in the brain that support cognitive function are called neurons. The term neurotoxicity here refers to toxic damage to these neurons. Many treatments surrounding transplant can be toxic to neurons. All of these processes together ultimately result in injury to the brain, which is then what causes cognitive impairment.

(08:50) Brain MRI scans can reveal lower brain volumes and reduced grey matter after transplant. To illustrate what I mean by brain injury, let's look at a couple of studies that were conducted in transplant recipients. This study measured brain volume in patients using a technology of brain MRI scan that you might be familiar with.

(09:07) The yellow orange areas show where brain volumes were significantly lower in patients after transplant compared to before transplant. This study focused specifically on a type of brain tissue known as grey matter. Grey matter is what does all the information processing in our brain. You can imagine that as grey matter is reduced, the brain's ability to effectively process information might be compromised. But fortunately, the brain is highly adaptive, and it can often adjust to injuries like this. The brain's ability to adjust or adapt will depend on many of those modifiable and non-modifiable risk factors that I talked about.

(09:54) Scans also reveal disruptions in white matter pathways in the brain after transplant. This next study measure the white matter tissue in the brain. The white matter is what makes up the pathways or connections in the brain, and it's responsible for communicating information between different grey matter regions. Grey matter is like your cell phone, and white matter is like the Wi-Fi or 5G network that allows your cell phones to connect to other cell phones.

(10:22) We see from this study, again, from the yellow orange areas, that there is a disruption of these white matter pathways after transplant. Now, I want you to remember that studies like this are based on findings across multiple patients. They represent the average outcome. This means that some patients will have little if any brain changes, while others may have very significant injury, and the average patient will potentially have the extent of injury shown here. Again, this injury and the effects that it has on cognitive function will depend on each patient's individual risk factors.

(11:06) Cognitive functioning can be assessed with neuropsychological measures. We typically evaluate cognitive function using neuropsychological assessments. A formal assessment usually involves an interview with a neuropsychologist to discuss the patient's symptoms and also get a little bit of their background history to get an idea about potential risk factors that they might have. The neuropsychologist will also often want to review the patient's medical records to get additional information that might be relevant to their cognitive functioning.

(11:37) The assessment then involves several hours of cognitive tests, and these can include paper and pencil type of tests and/or computerized tests that measure different cognitive skills. The assessment also includes evaluation of emotional functioning and stress. After all of that, the neuropsychologist will create a report for the patient that explains the results of the testing, detailing both cognitive strengths and also cognitive weaknesses, and will include recommendations for how to potentially address the cognitive difficulties.

(12:16) Typically, neuropsychological assessment is repeated yearly to track cognitive function over time. Neuropsychological assessment typically requires a physician referral. These referrals can come from neurology or neuro-oncology, but can also be made by a primary care provider. These exams are billed to health insurance.

(12:45) Neuropsychological testing has limits and sometimes doesn’t reflect the patient’s subjective experience of their cognitive functioning. One thing I want you to be aware of is that neuropsychology is not perfect. The tests sometimes don't have a lot of real world translation. For example, they are administered in a clinic where the distractions and stresses of life are greatly minimized. They might not always reflect your experience. These tests were also designed for more severe brain injuries that then we typically see in a transplant-related cognitive impairment, so sometimes they aren't sensitive enough to the problems that patients are having. It's also really difficult, as I mentioned, to get a baseline or a pretreatment cognitive evaluation in most cases. Sometimes the neuropsychologist just doesn't know how a patient was functioning before their diagnosis or before the treatments began.

(13:42) Many patients who struggle with cognitive effects after transplant have told me that their neuropsychological evaluation results were normal. This was very confusing, and so very invalidating to them. There are many explanations for this, it could be, again, the patient was above average functioning before treatment, and then declined to average or normal. Without that first assessment before diagnosis, it's hard to know this. Of course, a good neuropsychologist should be able to help interpret and address these kind of discrepancies between the testing results and what the patient has reported.

(14:23) Of course, not everyone is equal. Just like any other profession, neuropsychologist, some are better than others. A patient might have to take what is useful from the results and ignore things that aren't helpful or don't apply. The patient may also have to advocate strongly for themselves in order to be heard regarding cognitive effects. Fortunately, research in this area has really significantly helped increase understanding regarding these issues. There are focused efforts underway to improve the assessment of these cognitive impairment. These efforts do include an increased emphasis on patient report.

(15:06) Research evidence supports four types of intervention to improve cognitive functioning. Now, more importantly, let's talk about what can be done to help improve cognitive function after transplant. I'm going to discuss the current research evidence for four types of intervention: physical activity, cognitive training, cognitive rehab, and medication.

(15:28) Physical activity is by far the most important and can create new brain cells. Physical activity currently has, by far, the most research support for improving brain health. And aerobic exercise, how it works is aerobic exercise promotes neurogenesis, which means it actually creates new brain cells.

(15:47) I showed you earlier how some patients, after transplant, lose some of their gray matter. They're grey matter neurons. Once that neuron or brain cells injured and dies, it will never grow back. It's really important to be able to generate new ones.

(16:07) Physical activity improves heart health and many functional capacities. Physical activity also improves cardiovascular function. The brain, I mentioned before how the brain uses most of our energy, it also requires 20% of the body's oxygen, which is, again, the largest amount of any organ. Therefore, cardiovascular function is really critical for brain health.

(16:30) Physical exercise has been shown to improve fatigue, and it also improves functional capacities such as our stamina, range of motion, physical strength, and flexibility. Those things aren't necessarily directly related to brain health, but definitely to overall health, which in turn impacts our brain. Physical activity has also been shown to reduce the risk for cancer and also neurological illnesses like Alzheimer's disease. It is an overall really excellent intervention.

(17:10) In this study, my colleagues and I showed that rats who were treated with radiation have significant damage to white matter pathways. However, you can see here that the rats who are allowed to exercise have significantly more white matter pathways compared to the rats who are sedentary after radiation treatment. The exercising rats also had significantly better cognitive function than the sedentary rats.

(17:42) Guidelines recommend 150 minutes per week of moderate intensity exercise. These are the minimum physical activity guidelines based on the research evidence for promoting brain health, so 150 minutes per week of moderate intensity exercise. That is, for example, 30 minutes per day for five days or however you want to spread that out. Moderate intensity activities would include things such as walking, riding a bike, or gardening is just a few examples. Or you could do 120 minutes per week of vigorous intensity, such as jogging or high intensity interval training, or, of course, some combination of moderate and vigorous intensity exercise per week. This is what will promote that neurogenesis that is so good for your brain.

(18:34) Even gentle yoga and stretching exercises have benefits. Some individuals have physical limitations or other limitations. They're not able to engage in moderate or vigorous physical activity. Fortunately, several research studies have shown that even gentle yoga or stretching exercises can improve memory and attention function. Really, the important thing is to stay as physically active as is possible for you, and to do so regularly and consistently.

(19:08) Cognitive training involves many types of brain exercises. Cognitive training refers to exercises for your brain, or in other words, their mental activity. This activity can take many forms, including computerized games or exercises that are designed to help you practice certain skills, such as memory, attention, and problem solving.

(19:28) You've probably heard of these brain games that are available online. There are various different companies who provide these. I have known patients who really like those and find them very useful, and others who just don't like them at all. It's an individual thing as to whether or not computerized training is for you.

(19:53) Studies show benefits from computerized cognitive training programs. This is a study of healthy adults who completed a computerized cognitive training program. The colored areas on these brains show the improvements in brain function after that cognitive training. You can see that the training had really widespread effects on improving brain function. This is from one of the studies I showed you before of brain changes after transplant. I've circled the areas that overlap with the cognitive training improvements that were shown in this other study. Even though this other intervention study was not done specifically in transplant recipients, it shows the potential to improve function in the areas of the brain that are affected after transplants. These computerized cognitive training programs usually cost money. The jury is still out in terms of how well they work across different people and how long those benefits last.

(20:58) Another option is active journaling which engages multiple cognitive skills. There are many other things you can do instead of cognitive training on a computer. One activity that I highly recommend is what I call active journaling. This involves writing about events, thoughts, and feelings with a particular emphasis on analyzing, interpreting, and integrating what you write. You write it as if someone is going to read it and grade it for how concise and organized it is, how well it expresses and explains, including the use of proper grammar and spelling.

(21:34) When you write in this way, you engage multiple different cognitive skills, including attention, memory, organization, reasoning, language, and motor skills. Research has shown that people who write in this way have much lower risk for Alzheimer's and other types of age-related brain diseases. It seems to be a really great way to improve brain health and also protect the brain against future problems.

(22:05) Here are some examples of things you could write about in an active journal. What inspires you, and why? What interactions did you have with others? What did they mean to you? What new things did you learn from a talk given by Kesler, for example? What do you think about certain events that are occurring in today's world? What ideas you're having? What do you think about certain people, and why?

(22:34) It's more than just writing what you did for the day, but really thinking about things and that's what's going to exercise your brain. Even though you should write as if someone were going to read your journal and grade you on it, you, of course, don't actually ever have to show your writing to anyone.

(22:56) You should feel free to write whatever you want. These journal entries don't have to be limited to factual life occurrences. Creative writing, such as poetry or short stories can also be very effective mental exercise. You don't have to have any previous creative writing experience or training. Like I said, you can write whatever you want. The goal here is to exercise your brain in this way. Other ideas for creative writing include taking an event from your past that you wished had gone differently or writing about an event that takes place in your future, how do you envision your life one year from now or 10 years from now. To be effective, it's important to write in your journal regularly. It doesn't have to be every day, but you should find a schedule that you consistently stick with.

(23:54) Learning a second language or playing a musical instrument also has benefits. Learning a second language is another very effective mental exercise. It promotes neuroplasticity, which is the formation of new connections, so it helps with white matter pathways. This can also improve the brain's resilience. Language training has been shown in research studies to increase memory and also concentration skills. It's important to note that you don't have to become fluent in a language to experience the brain health benefits of language learning, even learning some very basic vocabulary or phrases, and then practicing these regularly can be very helpful.

(24:32) Music is a type of language and it also engages the mathematical centers of our brains. It results in increased neuroplasticity, and it's also neuroprotective. Again, you don't have to become a rock star and go on tour with a band in order to benefit from this very effective mental activity.

(24:54) Our brains remain plastic throughout our lives and can benefit from many types of cognitive training. It's also never too late to engage in these types of mental exercises. Our brains remain very plastic throughout our entire lifespan, and so they can always be improved. I know many people who have learned to play musical instruments later on in adulthood.

(25:14) There are lots of other activities that you can do for getting mental exercise, crossword puzzles, visiting museums, watching educational programs, participating in any kind of social discussion or group or club. Social interaction with other people is really good for your brain, playing board games or chess, reading, doing original art or craft work, taking a course, anything that keeps your mind active.

(25:43) The best activities are ones you enjoy and are done regularly and consistently. The important thing about mental activity is that you engage in it regularly and consistently. You should choose activities that you enjoy, because then you'll be more likely to stick with them. They should also be challenging, but in a Goldilocks kind of way, meaning that it shouldn't be too hard, but also not too easy.

(26:07) One thing to be aware of in terms of mental exercise is that you don't always notice a major change in your cognition right away. Many people do notice some over time. Again, it's different for everyone. This is often true physical exercise, too. You don't always lose weight or get six pack abs from exercising. We know that the benefits to our health are there, even if they aren't super obvious. The thing that you have to trust in is that mental exercise increases your brain's resilience and reserves. This is like putting money in the bank. If something happens with the economy, you will be more protected if you have savings. The same thing applies for the brain, mental, and physical exercise increase the savings that you have in your brain think.

(27:02) Cognitive rehab is a more formal, in-clinic program provided by occupational therapists or other specialists. Cognitive rehab is often confused with cognitive training. What rehab refers to and is a more formal in-clinic program, and it might actually include cognitive training, but it tends to focus more on compensatory strategies, workplace accommodations, and other functional support.

(27:24) Cognitive rehab is typically provided by occupational therapists or even some neuropsychologists. It usually requires a physician referral and is billed to your health insurance. The problem with cognitive rehab is that it's just not widely available. It can often be really difficult to find. If physical and mental exercise on your own is just not working, it might be something to consider.

(27:54) Rehab teaches compensatory strategies and provides support while the brain recovers. What do I mean by compensatory strategies? Well, there are some of these things you can actually do on your own, as well as within a cognitive rehab program. These include using devices such as a notebook planner, or smartphone to cue, remind, and alert you to things that you need to keep track of and remember. It also involves what we call managing situational demands, such as giving yourself more time to do things and doing only one thing at a time, rather than trying to multitask.

(28:30) The main concept here is that cognitive impairments mean that your brain has been injured. With any injury, that needs time to heal. While it's healing, it needs extra support, because it just can't function in the same way as when it's not injured. It's just like if you broke your arm. You probably should not be doing a boxing class or lifting really heavy weights with that object, with that arm. You'd probably be in a cast or some type of brace to support it and protect it while it heals. That's what compensatory strategies are. They're like a brace for your brain. They can be super frustrating, for sure, because no one likes to feel dumb or incapable or they're slower and have to do things in a different way than they did before. It's important to be gentle with your brain so that it doesn't injure further or slowdown in its recovery, just like how you would be gentle with and protective of a broken arm.

(29:36) Patients returning to work may require accommodations and supporting paperwork from their medical team. Patients who are planning to return to the workplace following transplant may require some accommodations if they have cognitive difficulties. Patients with cancer or any disease related cognitive impairment can be protected under federal law, including short and long term disability benefits. This can include support for when you are not able to return to work, as well as workplace modifications for when you do. For example, reduced hours or workload, relocating your work area to a quieter place, or partnering with a colleague for extra support for a period of time are a few examples. The specific modifications will depend on your individual situation.

(30:22) Disability qualification and workplace accommodations typically do require some supporting paperwork from your physician, your neuropsychologist, or some other qualified provider. Then these applications are reviewed to see if they meet the guidelines for approval.

(30:43) There are medications and supplements for cognitive impairment that help some people but they have side effects and clinical trials show mixed results. People often ask me about medications for cognitive impairment. There are stimulant medications like Adderall, Concerta, Ritalin, and many others that can often help in the short term with attention concentration and fatigue. You have to keep in mind they do have side effects, such as insomnia and anxiety, which sometimes can end up being worse than the cognitive problems in some cases.

 (31:11) I will also tell you that the clinical trials for cancer-related cognitive impairments using stimulant medications have not been super impressive thus far. Based on my experience and those of my colleagues, these medications can be really helpful in some cases. One thing to keep in mind is that these clinical trials have used neuropsychological testing to determine the effectiveness of the medications. As I mentioned before, sometimes these tests are not sufficiently sensitive to the effects. These medications are something to discuss with your physician, especially if you're having a lot of fatigue, in addition to cognitive problems.

(31:56) There are several supplements that are believed to help improve or support brain health, including Omega-3s and gingko biloba, for example. The evidence for these is pretty inconsistent, but there also have just been too few studies. There's not enough studies done for us to really know. Again, we have the same problem, as with the stimulant medication clinical trials, and that the cognitive tests used to evaluate their effectiveness might not be sensitive enough. I, honestly, don't know enough about supplements to make an intelligent recommendation. I have talked with several patients who find them useful. I would definitely discuss it with your physician if you're interested in trying it.

(32:46) Physical and mental exercise is the best “medicine” and patients are encouraged to schedule these activities on a regular basis. Overall, based on the entire body of research evidence to date, my primary recommendation is to combine physical and mental exercise. Physical activity, again, generate new brain cells, but about half of these actually die off after a few days.

(33:06) However, if you're also mentally active, it helps these new cells become integrated or what we call wired in to the rest of the brain. It's really the combination of these two, that's the best bet for your brain health. This doesn't mean doing them at the same time, like running on the treadmill and doing computer games, but just incorporating both of them into your routine in a consistent manner. These are both lifestyle changes. I know they can be really difficult to incorporate if you're not used to doing them.

(33:42) I always suggest to patients that they actually schedule time for these in their phones, with an alert just like any other appointments. This is tough for everyone. I struggle myself with these things, but anything you can do will be better than not doing them at all. If you can only get in five minutes a day of each of these things, that is definitely better than zero minutes.

(34:11) To summarize the key points, about two out of five transplant recipients will experience chronic cognitive problems on average.

(34:21) Cognitive problems after transplant result from injury to the brain that is caused by the disease, as well as the treatment, as well as stress and other factors involved in undergoing transplant. Each person's experience is different. These differences depend on certain risk factors, some of which can be changed. It's really important to work on those as much as possible.

(34:48) Regular and consistent physical and mental activity is really the best treatment for cognitive problems following transplant. These activities can both strengthen and also protect your brain and are really good for your overall health as well.

(35:07) If you're interested in further information about cognitive effects or including current studies we have going on in this area, please visit our website, you can scan this QR code with your phone or I have our website listed here. Now let's hear what questions you have for me.

Questions & Answer Session

(35:30) [Sue Stewart]          Q & A. Thank you,  Dr. Kesler. That was a great presentation. I learned quite a bit. I think your explanation of grey matter and white matter and why all that makes a difference and how it influences the way you think was really clear and very helpful.

(35:44) We do have a lot of questions. I'll try to get to as many as we can. Starting with this gentleman who said he's 19 months out from transplant and is continuing on oral chemo meds. He has slight struggle expressing certain words to complete thoughts. He's wondering if this will be chronic if he remains on this medication.

(36:09) [Shelli Kesler]      Well, it's really hard to say individually. It really depends on each person's individual risk factors and resilience factors also. Everyone is very different. We do know that the more intense the treatment is or the longer that it goes on, it can be associated with some increased chronicity of treatments. I'm afraid I can't say for certain based on an individual case.

(36:48) [Sue Stewart]      Alright. We've got a couple of people that asked the next question. They want to know, if you are a long term transplant survivor, are you at a higher risk for dementia and/or Alzheimer's disease?

(37:02) [Shelli Kesler]      There have been some studies that suggest that if you've had intensive chemotherapy, that there is potentially an increased risk for Alzheimer's disease. Based on my studies of that literature and also the studies we've conducted, I would say no, and it really is this interaction between, again, your genetic variation. There's a genetic variant called APOE-4 that is highly associated with Alzheimer's disease and other neurodegenerative diseases. It really turns out, when you look at it more closely, that it's the patients who have that genetic risk factor and also get chemotherapy that are probably at the most risk. It's the interaction of those two risks that is leading to that finding. Chemotherapy alone doesn't not seem to cause Alzheimer's disease.

(38:04) [Sue Stewart]      Good to know. The next person wants to know whether you think that art therapy can help with cognitive healing.

(38:16) [Shelli Kesler]      I do, absolutely. I mean, I've seen that in many people with cancer, without cancer, improve their cognitive abilities, do definitely. It's a very good way to exercise your brain.

(38:37) [Sue Stewart]     The next person wants to know, and I think she's referring to the slides you were showing where there was a yellow damage on the brain, if a brain MRI were to be done, say, three weeks after transplant, are the images that you showed on those slides what's to be expected? Or is that the exception to the rule?

(38:59) [Shelli Kesler]      That is an average of a whole bunch of people's MRIs together. If you did a MRI of one person, you probably wouldn't see that for a couple of reasons. For one thing, an MRI that you get in the hospital or clinic as part of your treatment is not the same type of MRI that we're doing here. These are our special MRIs that are done for research that are particularly designed to look at grey matter volume or white matter pathways. They aren't designed for doing individual diagnosis. If you've got one, you wouldn't see anything interpretable on that scan. If you got an MRI within that time period, would not show that.

(39:56) [Sue Stewart]     Alright, the next person wants to know if you recommend any particular computerized brain training program and whether computer games work as well.

(40:08) [Shelli Kesler]      There is a lot of research, it's mostly focused on age-related cognitive impairment and hasn't involved cancer so much to date. There's a lot of overlap between those two. I think that applies. There's a lot of research suggesting that computer games, like PlayStation, Xbox, can really be very beneficial for your cognitive function. It depends. If you don't like those games, then it's probably not going to be very useful to you. There are many people who have studied this and showed that those can be very helpful.

(40:46) In terms of if I recommend any, I really can't because I haven't studied all of them. I don't know all of what's out there. I think the important thing, they're all kind of different in terms of what kinds of games they provide to you. All of them have free trials. My advice is to try a few of them on those free trials and see which one you like best, because they are all very different in terms of their interface and what kind of games they have. I've heard from patients that some are really frustrating and they don't like the games, or some have a really hard interface. It's important to kind of try and figure out which one you liked the best before you go with one.

(41:37) [Sue Stewart]     Alright, I think this next question is something everybody can relate to. What is the best way to remember computer passwords? Every account I have has a different password.

(41:47) [Shelli Kesler]      I have the same problem, always forgetting my passwords. I use a compensatory strategy for that. I use the apple key chain, which remembers all of my password for me. There are a lot of resources for that. PC has it. There are different apps you can get that will keep track of those for you. It's just important to have one that's encrypted, and so that somebody can't hack that and get all of your passwords. That is what I personally use and what we recommend to our patients to do and people have found it to be the most useful, is to just keep them all in one place.

(42:40) [Sue Stewart]      Alright. The next questioner wants to know if there are any specific drugs used in transplant that are known to affect cognition, and specifically, he wants to know, if tacrolimus affects cognition.

(42:53) [Shelli Kesler]      I don't know about that one, particularly, and again, there has not been enough research in this area on specific drugs. The one that we know a little bit about is melphalan. That is associated with a lot of neurological issues. There's kind of this issue where people get a combination of drugs sometimes, and different people can get different drugs. It's been really hard for us to study which one is the culprit. We're trying to do this in animal models to try and figure out which ones are the most toxic. Currently, I don't have an answer for that.

(43:37) [Sue Stewart]      All right, this person wants to know whether crossword puzzles help brain cognition.

(43:44) [Shelli Kesler]      They do, they do. It's a matter of if the crossword puzzle is real easy. That's probably not going to help too much. If it's moderately challenging, you have to think about things, then that is, for sure, exercising your brain.

(44:01) [Sue Stewart]      Okay, this person is referring to the discussion we had about journaling. She wants to know whether writing on the computer works as well as writing physically with your hands.

(44:13) [Shelli Kesler]      Yes, yes, both of them. Each one of them are very good. They have slightly different advantages. On a computer, you can obviously write more. When you write with your handwriting, that exercise is a little bit more of your motor function. Typing is also a motor ability. Both of them work really well. It's just a preference.

(44:42) [Sue Stewart]      The next person wants to know if you're familiar with the 12-step program to improve cognitive abilities. If so, if you could talk about it a bit.

(44:52) [Shelli Kesler]      I have not heard about that. I'll have to look into that.

(44:59) [Sue Stewart]      Okay. How do you know if cognition and the decline you're experiencing i cognition is related to transplant or age?

(45:14) [Shelli Kesler]      There are a couple ways that we try to figure that out. One is the neuropsychological assessment, those tests are normalized for age. If you score low on those, that means that you're scoring lower on those than what would be expected of someone of your same age, and also education level. That's one way we look at it. In research studies, we look at it by comparing people who are of the same age, comparing a patient group to a group who is the same age. That's the other way. As an individual, you can compare yourself to your peers. How are your friends? How do they seem to be doing in terms of their memory or their cognitive functioning? Do you seem like you're not as good as them? Then that would be a sign that it fits due to something other than age.

(46:15) [Sue Stewart]      Alright. Next question asks, is there a difference between a condition such as attention deficit disorder or ADD that one might have had anyways, as opposed to ADD type symptoms that might result from cancer treatments? Are they treated in the same way or differently?

(46:41) [Shelli Kesler]     They are two separate syndromes. ADD has a different mechanism, which is that the frontal lobe is not developed well enough, and so it's under stimulated. The person has to externally stimulate to get that brain activity going. Whereas attention deficits occurring as a result of cancer or transplant or some other disease, is due to an injury to the frontal lobe. They have very different mechanisms. They can be treated in a similar way in terms of that we treat the symptom, which is attention deficit. Because, like I said, we can't regenerate brain cells. It also depends on the person and what their history was and also what type of attention deficits they have. Yes, it can be treated the same in some situations.

(47:50) [Sue Stewart]      This person would like to know, can you still improve your brain 10 years out after transplant?

(47:57) [Shelli Kesler]      Absolutely. Most of the cognitive training and physical exercise, most of the intervention studies that have been done so far, in transplant, and other related areas have been done in long term survivors, because that's who we're most concerned about, is the ones who didn't improve on their own after a year or two. It definitely is. Like I mentioned, the brain remains very plastic, meaning that it's still very adaptable and can still learn new things. That adage that you can't train an old dog new tricks is totally false when it comes to the brain's plasticity. You can always improve your brain function, no matter how old you are.

(48:45) [Sue Stewart]      Okay, this individual wants to know whether Strattera, which is not a controlled substance like Adderall has been known to be helpful or is it not as effective?

(48:54) [Shelli Kesler]      Unfortunately, I don't know of any studies that have compared those or have looked specifically at Strattera. I'm not a physician. That would be a question I would ask your physician for an opinion about.

(49:16) [Sue Stewart]      In a similar, but different thing, this gentleman wants to know what's the effect of cannabis on cognition, either positive or negative.

(49:27) [Shelli Kesler]      The study there has been a bit mixed. Some people have a worsening of memory and attention issues with cannabis use. I think we don't yet know enough about, again, the combination of risk factors and who is getting those issues or how long they might last. It does seem to be a risk factor that you have to take into consideration. All these things have to be balanced. Like if you're having a lot of pain and you can't sleep, and so you're taking cannabis for that, and then you notice, oh, my attention and memory is not so good.

(50:13) Well, if you don't sleep and you have a lot of pain, those things are going to get worse also. It's sort of Catch-22 situation there. The research in that area is not super clear. There is this known risk for memory and attention issues with cannabis, but it's just not known how long it lasts or who it affects.

(50:37) [Sue Stewart]      Next question goes to how long does cognitive process last? What is the typical duration, a year, indefinite?

(50:47) [Shelli Kesler]      Well, on average, again, and it depends on which kind of what population you're looking at and what tests they got. The studies are a little bit different. The one that I showed the average was five years. Some will have less, some will have more.

(51:14) [Sue Stewart]      Alright. This individual says that during the conversation, she can't concentrate like she used to. Her mind is thinking about many other things while she's trying to listen. Is this a symptom of ADD, attention deficit disorder?

(51:33) [Shelli Kesler]      It sounds like it's attention deficit from transplant or from the disease. If you didn't have those problems before, then it's probably not "ADD." This is confusing, because ADD is a syndrome that usually starts in childhood that is associated with attention deficit problems. Like I said, it has a different mechanism that causes it. If you have those problems after transplant and you didn't have them before, then we would probably think that it was transplant related. It's not ADD. That's not the diagnosis. The diagnosis would be neurocognitive disorder due to its medical conditions.

(52:20) All of that is just a bunch of words, meaning the same thing, which is that you have problems with attention. You wouldn't probably get a diagnosis of ADD if that's what you're asking. It's not the same thing. It's not that. It's not the ADD syndrome. It's the transplant related cognitive impairment syndrome.

(52:45) [Sue Stewart]      Do you know if CAR T-cell therapy, which is a newer therapy to treat some cancers, whether that also can cause memory loss?

(52:54) [Shelli Kesler]      It can, yes. It's not known the extent to which CAR T or other immunotherapies results in cognitive problems that some people ... CAR T, one of the things that it does is cause a really big increase in inflammation. Some people can't speak for a time after that or they have a lot of memory problems. A lot of those so far have resolved. It's so new that we just don't know the long term consequences of that. Yes, it can definitely result in cognitive changes.

(53:37) [Sue Stewart]     This woman says that she's glad that you included stress as a significant toxic contributor to cognitive deficits, what she wants to know is does research say what is most effective in managing stress?

(53:54) [Shelli Kesler]      Physical activity is probably number one. Number two would be relaxation exercises. Taking 10 to 20 minutes out of the day to just meditate, relax, do some guided type of relaxation, exercise, breathing, all of those kind of alternative integrative medicine approaches are really what get your physiological response to stress and lower those. Because what happens is, when we're chronically stressed, our body can no longer lower those factors itself.

(54:38) Stress is related to inflammation and increase in cortisol and other hormones and factors in our body that can be really toxic when they remain elevated over time. When we get chronically stressed, our body loses its ability to regulate those things by itself. Then we have to do it by relaxing ourselves and the best way to do that to get those factors down is physical exercise, but also, relaxation training meditation.

(55:16) [Sue Stewart]      Alright. This person wants to know whether there's a book that you can recommend that does a good job dealing with topics like we're discussing here. I presume she needs a book that talks about the same issues that we're talking about here.

(55:33) [Shelli Kesler]     Well, I published one a few years ago, it's outdated now, but it is on Amazon, called Improving Cognitive Function After Cancer. It talks about a lot of this stuff. There's another one, and I'm totally blanking on the name of the person who wrote it. I can get it to Sue. She can get it out to everyone. It's, I think, called dealing with chemo brain. It's a little bit different. It's not as general. There aren't a lot. There are only a couple that I can think of.

(56:13) [Sue Stewart]      Alright, and then speaking of getting things to me, we have another person who wanted to know if you could provide links or names of the studies that talked about the gray matter and injured white matter pathways in the brain.

(56:26) [Shelli Kesler]     Yeah. Those references are in the slides. They're in the slides. They're like a lighter font. If you download the slide, that references is definitely in those slides.

(56:38) [Sue Stewart]      Yeah. It's the resources tab above the main screen, is where you can download those slides. Alright, what causes an increase in white brain matter?

(56:59) [Shelli Kesler]      In white brain matter. White matter is the pathway in your brain. The best way to increase those is through mental exercise, because when we are really mentally engaged, our white matter pathways reorganize themselves. That's how we store information that makes our information processing more efficient and effective. The best way to do that is do mental stimulation.

(57:35) [Sue Stewart]      Then I think we will wrap it up with a question from a nurse, since we were told by our keynote speaker to honor nurses in all ways that we can. She said she was a nurse prior to transplant and is looking to go back, but she's fearful of 12-hour shifts with her decline in cognitive ability. She wonders, are there workplace requirements to accommodate shorter shifts for people like her?

(58:05) [Shelli Kesler]     They are, according to federal law, and they're required to make reasonable accommodations. It depends on supervisors. I've had some patients who talk to their supervisor about this. Their supervisor just went ahead and helped them do accommodations. Others have had to go through the process of getting like a neuropsychological evaluation or getting their physician to fill out the paperwork, and the physician recommending a shorter shift. It depends. Yes, they are required to make reasonable accommodation under federal law. Sometimes you have to have the paperwork to get them to do that.

(58:52) [Sue Stewart]      Closing.  I might also add later in the week, I forget which day it is, there is a talk on employment rights by Joanna Morales. If you look at the agenda, I want to say it said maybe Wednesday or Thursday. She will have a lot of information about your rights in terms of seeking and getting accommodations. Unfortunately, we are out of time. It's been a fascinating discussion. Thank you, Dr. Kesler. Thank you, the audience, for some really excellent questions. I know this is a very hot topic among transplant survivors, one that we deal with every day. I think you gave us some really good suggestions for how to manage it and where to go and seek help. With that, I will close this session. Thank you, everybody, for attending.