Living with Cognitive Changes after Transplant and CAR T-Cell Therapy

Transcription:

[00:02] Moderator: Good day, everyone. Welcome to the workshop, Living with Cognitive Changes after Transplant and CAR T-Cell Therapy.  My name is Michael and I will be your moderator.

It is my pleasure to introduce today's speaker, Dr. Anna Barata.  Dr. Barata is an Assistant Professor of Psychology at Mass General Brigham Cancer Institute and Harvard Medical School. Her research focuses on examining patient-reported cognitive outcomes and testing psychological and behavioral interventions to improve the quality of life of both patients and care partners. Please join me and welcome Dr. Barata.

[00:43] Dr. Barata: Thank you so much, Moderator, for this very kind introduction.  I would like to welcome everyone and thank BMT InfoNet for the kind invitation. I'm excited to discuss cognitive changes following CAR T-cell therapy and transplant.

[01:22] Overview of Presentation. During today's presentation, we will begin with an introduction and explain why addressing this topic is important. We will also describe how changes in memory, thinking, and overall cognitive function may feel for patients who experience them, and review the reasons these changes occur after treatment with transplant and CAR T-cell therapy.

We will also describe what we know from studies and the literature regarding changes in thinking and memory for patients treated with transplant or CAR T-cell therapy.

At the end of this session, we will review strategies to support changes in thinking and memory after treatment.

We will conclude with some comments and discussion, and there will be ample time at the end for any questions you might have about this topic.

[02:36] Cancer treatments, such as radiotherapy, chemotherapy, transplant, and CAR T-cell therapy, target the disease, but they also affect the whole body, including the brain. As a result, patients might experience changes in their thinking or memory, notice they are forgetting small things, or think more slowly than they used to.

These changes can be distressing. Talking about them with other patients and families and addressing them at symposia, such as the one we are currently attending, are helpful.

[03:21] Since cognitive changes are very common and often improve over time, they feel different for patients who experience them. Generally, they include forgetting small things, such as conversations and appointments, trouble concentrating, thinking more slowly than they used to, difficulty handling multiple tasks at once, or feeling that tasks take longer than they used to. This is also known as feeling mentally tired.

These cognitive changes are often referred to as “chemo brain” or “brain fog”. We generally hear from patients that they feel like their brain is temporarily running a bit slower or less smoothly than usual.

[04:21] Changes in memory and thinking after transplant or CAR T-cell therapy can be caused by the cancer or treatments that cause inflammation, changes in the immune system, side effects of medications, fatigue, poor sleep, and/or stress.

There are several reasons why changes in memory and thinking can occur after CAR T-cell therapy or transplant.

Patients have received strong treatment, not only transplant or CAR T-cell therapy, but also treatments prior to transplant or CAR T-cell therapy, such as chemotherapy or radiotherapy. These treatments target the disease, but also affect the whole body, including the brain.

Some cancer treatments, or the cancer itself, can cause inflammation in the body. Inflammation is part of how the body responds to stress or injury. It can affect how the brain works, making it harder to think clearly or remember things.

Likewise, changes in our immune system may affect the brain, since cancer and its treatment can alter how the immune system functions. When the immune system is more active or out of balance, it can send signals that affect the brain, making it harder to concentrate or remember.

It's also common for some medications to have side effects that affect thinking and memory. For example, some medications for pain, such as opioids, or medications to prevent nausea or to promote sleep, make patients feel that their brains are a bit slower or less focused. This is a common side effect of some medications, but it often improves once the medication is completed or adjusted.

Other issues that might affect changes in thinking and memory are fatigue and sleep problems. Both are common in cancer patients treated with transplant or CAR T-cell therapy, and we know that when we feel tired or are not sleeping well, it is much harder to think clearly.

Stress, worry, or feeling overwhelmed can also consume a lot of mental energy, leaving fewer resources for thinking and concentration.

[06:38] While many of the factors that can lead to changes in thinking and memory at first glance might seem quite different, they are actually closely linked and share a common underlying mechanism, which is the interaction between the brain and the immune system.

Both transplant and CAR T-cell therapy activate the immune system to fight cancer. And when the immune system is activated, it releases chemical messengers called cytokines that help coordinate the body's response against cancer.

However, these cytokines can also affect how brain cells communicate, leading to changes in cognitive symptoms, such as the “brain fog” or “chemo brain” we just described. These effects are usually temporary and improve as the immune system calms down and the body recovers.

[07:39] In practice, though, what matters is how all these cognitive changes show up. We typically approach cognitive changes in both clinical practice and research.

The first approach that you see here on the slide is the patient's perceived- or patient-reported cognition. This is what patients tell clinicians or researchers about how their thinking works and their experiences in daily life, including whether they feel more forgetful or distracted, or think more slowly than usual.

The second approach is to use a battery of neurocognitive or neuropsychological tests, which include structured tasks we ask patients to complete to help us know how patients are doing with memory, attention, learning, and thinking.

Both assessments are important because they provide us with complementary information. What patients notice in everyday life may not always be fully captured by neurocognitive tests, and neurocognitive test results may reveal subtle changes that patients do not notice in daily activities. Together, both assessments give us a more comprehensive understanding of cognitive function and its impact on patients’ daily lives.

Thanks to the patient-reported assessment or neurocognitive assessment, we can understand how patients are doing in terms of memory, attention, concentration, slower thinking (also called processing speed), and how patients are doing in terms of multitasking, planning, or problem solving (also called executive function), difficulties recalling words (also called verbal learning), or feeling mentally tired.

We will review all these concepts in the following slides.

[10:04] So let's now describe how thinking and memory changes after transplant might feel for some patients.

I believe that yesterday some colleagues already discussed what a transplant is and what it involves, so I'm just going to touch on this very briefly to provide some context and understanding of what happens at the cognitive level.

[10:29] There are two types of transplants. One is an autologous transplant, in which patients receive their own cells, and the other is an allogeneic transplant, in which patients receive cells from a donor.

In both cases, patients receive high doses of chemotherapy and sometimes radiation as well, which helps create space in the bone marrow for new cells.

Thereafter, patients are infused with the cells, which travel to the bone marrow where they begin to grow and rebuild. 

Thereafter, the immune system will slowly start to work again.

During this period, patients may present with complications, such as infections, since the immune system is still very weak, or with graft-versus-host disease, a condition seen in patients treated with an allogeneic transplant in which donor cells react against the patient’s body.

Patients undergoing transplant might have other risk factors associated with an increased risk of cognitive changes, such as having received and might receive additional high-dose chemotherapy or radiotherapy, which can impact the brain cells.

Following cell infusion, the immune system can become very active, sometimes causing inflammation in the body and brain. There are also some complications associated with transplants, such as infections and other issues.

Some medications have side effects that affect patients' cognition, such as those used to prevent rejection or graft-versus-host disease. Some medications used to treat inflammation may also affect cognitive function, as may some medications used to treat pain, nausea, or to help sleep.

We know that patients treated with transplant often present with fatigue, sleep disruption, distress, or symptoms of anxiety or depression, which affect cognitive function. 

I'm going to review some studies about cognitive outcomes after transplant.

[13:11] What we know from the literature is that before transplant, it's common for some patients to experience changes in one or more of the following domains: attention, difficulty with planning, organizing things, or staying focused for a while; difficulty finding words when speaking, or difficulty recalling specific information. After a transplant, these changes often become noticeable for a while. 

Many patients describe feeling foggy or not thinking as clearly as usual during the first days or even the first weeks following infusion of cells. But for most people, these changes gradually improve over time, to the point that thinking skills may return to levels close to pre-transplant around one year after transplant, although recovery may vary from person to person.

[14:11] In the next slide, I'm presenting one of the most important studies conducted on this topic, which followed up on participants' cognitive function up to five years post-transplant. This study was conducted a few years ago, but it's one of the most important studies on this topic. 

The researchers asked participants to complete cognitive measures prior to transplant, then followed them up at different time points for 5 years after transplant.

[14:45] At the top of the left side of the screen, you can see results describing how patients were doing in terms of planning, organization, and focus.

As you can see in the first graph, participants exhibited some impairments prior to transplant and up to day 90 after transplant, but began to improve afterward, such that five years post-transplant, they exhibited better outcomes than prior to transplant.

[15:12] At the bottom of the screen, still on the left side, you'll see another way to look at the data: almost 50% of patients never exhibited impairments in this domain.

Around 40% exhibited some impairments during these five years, but they then recovered to pre-transplant levels, and less than 20% remained impaired at five years post-transplant.

[15:37] On the right side of the screen, you can see another domain these researchers examined: information processing speed. This is how quickly our brain takes in information, makes sense of it, and responds to it.

In this case, researchers found that prior to transplant, participants performed as well as other patients who never received a transplant.

In the weeks following infusion, participants exhibited some declines in this cognitive domain, but began to recover from day 90 onward, to the extent that at one-year post-transplant, they were doing as well as other patients who had never received a transplant. Recovery continued over time at five years post-transplant.

[16:25] You can see another way to look at the data in the graph below. Almost 70% of patients never exhibited impairments in information or processing speed during these five years following transplant. Around 40% were impaired at some point, and then they recovered. And less than 10% of patients remained impaired five years following transplant.

[16:50] The next slide provides additional context on what happens at the cognitive level after receiving a transplant. Here you can see the results for verbal memory. This is our ability to remember what we have heard, such as the threads of a conversation or specific instructions.

[17:12] Researchers found that prior to transplant or in the first weeks following transplant, participants exhibited impairments that began to improve by day 90 and then remained relatively stable over time.

[17:29] Another way to look at this data is that almost 50% of the patients never showed an impairment in this domain during the first years that the study lasted. Around 40% were memory-impaired and recovered, and around 20% remained impaired at five years post-transplant.

[17:48] Another domain that is important to consider is called hand speed and coordination. This is how quickly and smoothly our hands can move and work together. This skill helps us do things like write, type, or use our cell phone, or pick up small objects.

In this case, participants exhibited some declines during the first 90 days following transplant, then began to improve by day 90, performing similarly to before the transplant. Almost 70% of patients were never impaired, or if they were impaired, they recovered, and around 30 percent of patients remained impaired at five years post-transplant.

The good thing, though, is that these skills can often improve with practice exercises and, sometimes, additional support, as we will review later in this presentation.

[18:48] There is some variability in how cognitive changes affect patients, and this variability can depend on several factors, such as age. 

We know that older adults might be more sensitive to cognitive changes in thinking and memory.

People with fewer years of formal education might notice cognitive changes more than people with more years of formal education.

Patients who received an allogeneic transplant [cells from a donor] have a greater risk or experience greater cognitive changes compared to patients who received an autologous transplant, using their own cells.

The intensity of chemotherapy is also related. Stronger, more intense chemotherapy regimens can increase the risk of experiencing temporary cognitive changes. 

The presence of complications such as infections or graft-versus-host disease can also affect thinking.

Finally, overall well-being also plays a significant role. Fatigue, sleep, and emotional distress play significant roles in cognitive changes.

[20:07] Let's shift our attention to describe what happens with thinking and memory after CAR T. This cutting-edge treatment has some challenges but also has significant benefits.

Yesterday, a colleague of mine discussed CAR T-cell therapy, so I'm just going to review it briefly to provide some context for what might happen to thinking and memory after this treatment.

In CAR-T, the first step is to collect the patient's own immune cells. This process is called leukapheresis.

Next, these cells are modified in a lab to better recognize and attack cancer cells. While these cells are being prepared in the lab, it's common for patients to receive chemotherapy to help the new, modified cells work properly and more effectively.

Finally, the modified cells are infused into the patient and travel through the body to find and attack cancer cells.

[21:12] While CAR-T-Cell therapy has dramatically improved outcomes in patients with hematologic malignancies, it also has a unique toxicity profile that is characterized by two hallmark side effects. 

The first one is cytokine release syndrome (CRS). This is a common reaction that can occur when the new CAR T-cells become active and start attacking cancer cells. This causes significant inflammation and manifests as a flu-like syndrome that may include fever, malaise [generally feeling ill], anorexia, myalgias [muscle aches or pain], and other symptoms.

The second hallmark side effect is neurotoxicity or neurological side effects, which present with symptoms such as dysgraphia [difficulty writing], confusion, language disturbance, or agitation, among others.

These hallmark side effects are associated with inflammation, and therefore, researchers have been concerned about their impact on patients' cognitive outcomes.

CAR T-cell therapy can affect the brain and cause a strong activation of the immune system, cytokine release syndrome [CRS], and acute neurological toxicities [ICANS].

[22:35] Prior to CAR T-cell therapy, some patients may already feel stressed or anxious about receiving a new therapy and may experience changes in thinking and memory related to this stress, or to prior medications or chemotherapy that can affect cognitive function at this point.

Day zero is when the new cells are infused into the patient. It's common during the first week after the infusion for some patients to have mild confusion, headaches, dizziness, or mood changes.

One to three weeks following the infusion, some patients experience peaks in confusion, difficulty finding words, or difficulty speaking clearly, particularly if they have cytokine release syndrome or neurotoxicity. It's also common for some patients to present with fatigue, which is commonly associated with cytokine release syndrome.

The good news is that these symptoms usually resolve after week three, or even earlier, because cytokine release and neurotoxicity tend to resolve during the weeks following the infusion.

Although we know that cytokine release syndrome (CRS) and neurotoxicity usually occur following the infusion of the CAR T-cells, some researchers have been concerned or interested in learning how patients who are treated with CAR T-cells are doing in the long term.

[24:18] To understand how changes in thinking and memory occur long-term after  CAR T-cell therapy, we conducted one of the first studies to examine this.

We administered a battery of neuropsychological and neurocognitive tests to patients who were treated with CAR T-cell therapy, and assessed their performance in planning, organization, visuospatial abilities, memory, learning, and other domains. We then averaged these scores and derived a total neurocognitive performance score.

[25:02] When it comes to planning, organization, and focus, what we observed was that participants exhibited a small decline in this domain following the infusion of CAR T-cells. However, they also exhibited improvements from day 90 onwards.

[25:21] Now I'll refer to visuospatial abilities, which are at the bottom of the slide. In this case, participants exhibited small declines in visuospatial abilities over time. Even though it might appear significant on this graph, in clinical and statistical terms, this decline was relatively small.

We administered several other neuropsychological tests and averaged all the scores together to get a total neurocognitive performance score that you can see on the top left side of the screen. 

We found that participants treated with CAR T generally exhibited a small decline in cognitive functioning from before CAR T-cell therapy to day 90 after the infusion of cells. However, they improved from day 90 onwards, and this was statistically significant.

[26:18] In addition to examining objective cognitive function through neuropsychological tests, we also asked participants to fill out a questionnaire and inform us how they were doing in terms of cognitive function, what we refer to as perceived cognition or patient-reported cognition.

This questionnaire provided us with a global score, meaning how patients perceived they were doing globally, and specific scores about how they were doing in terms of memory, language, visuospatial abilities (for example, the ability to use a map or to orient themselves in a city,) planning, organization, divided attention (which told us about their ability to multitask), as well as their satisfaction with cognition.

[27:15] Participants did not report any change in global cognition or any cognitive domain from prior to CAR T through day 90. 

However, participants reported small impairments in global cognition, as well as in memory, language, organization, and divided attention, from day 90 to day 360, likely because this is when patients began to resume their prior activities, and some of them were also reporting high levels of stress.

[27:50] I want to share another study that we conducted recently, where we examined the percentage of patients who experienced improved cognition at six months following CAR T.

Patients who reported improved cognition are shown in green. Patients who reported that their cognitive outcomes were stable at six months, meaning that they didn't feel any change [shown in blue], and the percentage of patients who reported a small decline in their cognitive outcomes in six months after CAR T [shown in red].

Over 80 percent of patients said that their thinking, memory, and cognitive outcomes improved overall or were stable at six months after CAR T, highlighting that CAR T is a safe therapy when it comes to cognitive outcomes.

[29:14] Some participants reported declines in cognition or delayed memory recall, and this is the focus of our research as well: Why are these participants reporting this decline in functioning in these domains? 

It might be because, in CAR-T, specific individual factors can affect cognitive function in patients. We know that older patients, those with fewer years of education, and those receiving or who have received more prior treatments may be more sensitive to cognitive changes.

We also know that cytokine release syndrome and neurotoxicity may affect cognitive function, but their exact impact on long-term cognitive outcomes is still unclear. Some studies have found that cytokine release syndrome and its inflammation might affect long-term cognition, but other studies haven't confirmed these findings.

We know that participants with greater levels of fatigue, sleep, and emotional distress are more susceptible to experiencing cognitive changes following treatment.

[30:20] While cognitive changes are common, we also know there are strategies that might help to deal with changes in thinking and memory after transplant and CAR T-cell therapy. We will review them on the next slide.

[30:41] There have been several studies testing whether some prescription medications called psychostimulants are able to improve attention, memory, or thinking speed. However, the results of these studies have been mixed, meaning that some people have reported benefits, but other studies have not been able to confirm these findings. Therefore, the overall evidence for these medications is not strong or consistent at this point.

There have also been studies testing whether drugs to treat Alzheimer's are effective in improving memory and thinking problems in patients with cancer. However, they have not, as of now, been shown to be effective in improving memory and cognitive thinking problems overall in patients with cancer.

[31:39] Finally, there are also some lines of research examining whether some over-the-counter supplements, such as those listed on this slide, might improve cognitive outcomes after treatment in patients with cancer, but there is not enough evidence at this point to demonstrate a clear benefit, and in some cases, studies have shown no effect. 

Overall, we have not found medications that effectively improve cognitive outcomes in patients treated with a transplant or CAR T.

[32:18] There are some studies testing additional strategies called brain training.

Brain training refers to activities or programs designed to keep the brain active and engaged in different activities. This can include apps such as Luminosity, which offers games and exercises targeting memory, focus, and processing speed.

Some studies are testing whether everyday activities such as crosswords, puzzles, word games, and other activities can improve skills such as memory, language, attention, or reasoning. The idea is that these training activities might help keep the mind active and support specific skills. 

However, it's important to note that there are few studies in patients with cancer, and the evidence is still emerging. There is no strong evidence supporting its efficacy in patients with cancer, but it helps with mental stimulation.

[33:38] There are some strategies that are effective in improving thinking and memory.

The first one is practical strategies that might make daily life easier. This includes using notes, alarms, and calendars, as well as phone alarms, to remember important tasks or appointments.

It also helps to break larger tasks into smaller, more manageable steps and to focus on one thing at a time rather than multitasking.

Having regular routines can also reduce the mental effort needed to stay organized.

[34:19] The second strategy is lifestyle support. This plays an important role.

There are several randomized controlled trials, very well-designed studies, that have shown that physical activity improves cognition. Even light exercises, like walking, can support brain health.

We also know that getting good sleep and rest is important when one feels tired or fatigued. Fatigue makes thinking more difficult.

We know that staying socially and mentally active is important. Spending time with others or doing enjoyable activities can support overall cognitive well-being.

A combined approach of all these activities is much more effective than individual strategies.

[35:12] We encourage any patients, caregivers, or family members who are concerned about cognitive outcomes to bring them to the team to discuss.

It's important not only to discuss specific concerns, but also to discuss whether there is a sudden or worsening of memory, attention, or thinking; if confusion starts to interfere with daily activities, such as managing medications, following conversation, or handling everyday tasks; and if cognitive problems are persistent and do not improve over time.

Finally, it's important to bring any concerns about cognitive outcomes that might interfere with safety, such as cooking or driving, to the team.

[36:02] Summary of Presentation:

Transplant and CAR T-cell therapy can lead to changes in thinking and memory, particularly shortly after treatment. These changes are common.

The good news is that these changes tend to improve over time, although recovery might take months for some patients.

There is evidence that healthy habits, lifestyle support, and interventions help manage changes in memory and thinking after treatment with a transplant or CAR T-cell therapy.

[36:38] And with that, I'm going to conclude. Thank you all for your attention. I'll be happy to answer any questions you may have.

[36:47] Thank you all.

Question and Answer Session

[36:49] Moderator: Thank you, Dr. Barata, for an excellent presentation, especially for me, being a transplant survivor, I love it.  So, let’s take some questions.

[37:11] Have you noticed that a patient's memory and cognitive ability improve further out from transplant?

Dr. Barata: Yes, we’ve noticed that, and there are several reasons why that can happen. 

Transplantation might lead to increased inflammation, which tends to decrease over time.

Patients may also receive significant medications during transplant, and physicians might be lowering the dosages or deciding that the patient does not need to take specific medications. Therefore, patients might be experiencing fewer side effects.

So, it's common for patients to experience improved memory over time, and for their overall cognitive outcomes to improve as well.

[38:02] Moderator: How can you know the difference between chemo- and transplant-related cognitive issues and changes related to normal aging?

[38:24] Dr. Barata: This is a good question. Age itself is a contributing factor that affects all of us. We are all getting older.

Chemotherapy has side effects, and some of them may persist over time. So, chemotherapy, or chemo brain effects, might be contributing to age and all the other factors that we just reviewed.

So, age is a factor that we all face for cognitive changes over time. In addition, receiving chemotherapy can have side effects that may contribute to further changes over time.

[39:06] Moderator: How temporary are the effects on the brain?

[39:15] Dr. Barata: I don't think I can give a specific answer here because several factors affect how long these cognitive changes might last.

For some patients, they might last very briefly. For example, in CAR-T, some patients develop cytokine release syndrome or neurotoxicity, which can lead to cognitive symptoms. Once this cytokine release syndrome is treated, these patients might notice improvements in their cognitive function over time.

However, other cognitive changes might be due to other reasons, such as the lasting effects of chemotherapy, or even to other specific side effects in patients treated with a transplant. 

For example, we know that transplant patients might be on medications to prevent rejection of the donor cells for a period of time, and this might interfere with cognitive outcomes. In this case, changes in cognitive outcomes might persist longer than in a CAR T patient with cognitive changes due to cytokine release syndrome. 

So, I do not have a specific answer here.  It depends on the reasons that are causing these changes in cognitive outcomes.

[40:41] Moderator: Are you seeing memory getting better after transplant? I'm thinking years down the road, some things are better, and some are not. What are your thoughts?

[40:54] Dr. Barata: Again, this is a good question. It is totally reasonable that some patients experience improvements over time in their cognitive outcomes.

You may remember that I presented some graphs showing how specific cognitive outcomes were improving over time. Some patients may even notice that memory or cognitive outcomes are better three years after transplant than before the transplant. 

So, some patients might feel that cognitive domains improve over time, but others do not.

There is still a lot of research to do on this topic to better understand why memory might improve, and planning might not. This is an area of research. But the experience that this participant is sharing is known, and yes, it's true.

[42:07] Moderator: Will any diet or foods help restore cognitive function?

[42:17] Dr. Barata: Good question. There are some studies highlighting the importance of diet, but we don't have strong evidence from multiple randomized controlled trials. Randomized controlled trials are the type of study that provides the strongest evidence.

There have been some randomized controlled trials, but we don't have strong evidence from them showing that “this is the diet”. We know there might be specific nutrients associated with cognitive health, but we don't have evidence from systematic reviews or multiple randomized controlled trials to support this.

[42:55] Moderator: Do any supplements or vitamins also help? 

Dr. Barata: They might be helpful, but the evidence that we have comes from small studies, so I'm not going to say “let's take this one” or “let's take the other”, because there are no systematic reviews or a meta-analysis showing a specific supplement helps.

[43:29] Moderator: Do you notice any rebound effects with additional treatments? In other words, if you've had a transplant and then you were good for a few years, but then you had to go back on treatment, are there any rebound effects on cognitive outcomes?

[43:50] Dr. Barata: This is a good question, and a reality faced by some patients having a second transplant or for patients who have been treated with a transplant and thereafter are offered a CAR T-cell therapy.

Every time we add another treatment, we might be increasing the toxicity and the side effects, and therefore, there is a risk that this might also be impairing a patient's cognitive function. So, receiving a second transplant or receiving CAR T-cell therapy after the patient has been treated with a prior transplant might increase the chance of experiencing changes in memory and thinking.

But I want to make a point here. Adding an additional treatment may increase the chance of experiencing cognitive outcomes, but it's also super important to try to mitigate them. It's possible to mitigate them by adopting the lifestyle changes we just reviewed and keeping one’s mind as active as possible through mental activities. 

Physical activity is super important for managing fatigue; try to get good sleep, as these are all modifiable factors that directly impact cognitive outcomes.

[45:30] Moderator: Are there factors that existed prior to a person's illness or treatment that make them more likely to have cognitive changes after treatment?

[45:40] Dr. Barata: We know that age is associated with cognitive outcomes.

We know that educational level is associated with cognitive outcomes.

We also know that frailty, a concept I have not discussed here, is sometimes associated with how well a person feels. It might not only be affected by age, but now we have older patients who feel much better, who feel great for a transplant, and this might also be associated with improved cognitive outcomes.

Overall, patients' health status may predict a greater likelihood of preserving cognitive function after transplant or CAR-T.

[46:36] Moderator: Can speech therapy help with cognitive issues?

[46:42] Dr. Barata: Speech therapy may not only improve or preserve speech, but also work on issues such as staying focused and engaged in meaningful activities.

[47:29] Moderator: Have you studied or seen where a person's judgment, i.e., their spatial judgment or distance perception, is affected after a transplant?

[47:42] Dr. Barata: I might need additional context to understand this question. For example, some patients might experience confusion associated with the cytokine release syndrome, or some patients may present with delirium associated with infection after transplant. So, when one is confused, this affects the ability to be informed or to make informed decisions.

When it comes to spatial abilities, this is an outcome that we study in our research when we study visuospatial abilities, the ability to orient oneself using a map or to orient oneself in a city.

[48:46] Moderator: Have you seen any research that shows the cognitive effects are different between an allogeneic and autologous transplant or CAR-T therapy?

[49:05] Dr. Barata: Good one. We know that patients who are treated with an allogeneic transplant have a greater risk of experiencing changes in cognitive function than patients who are treated with an autologous transplant.

There are no well-designed studies comparing cognitive outcomes among autologous transplant, allogeneic transplant, and CAR-T-Cell therapy yet. But of course, this is an area of interest, and it will be the focus of research.

[49:43] Moderator: How long do the memory issues last, and does gender affect the issue at all?

[49:52] Dr. Barata:   We don't know a specific timeline to say that after three weeks, three months, or three years, memory is going to be improving, because it depends on several individual factors.

But we do know from studies that gender is not specifically associated with delays or faster improvements in memory. So, gender or sex is not going to predict how long these changes will last.

[50:29] Moderator:  Besides games, do you think that doing crafts like crocheting, knitting, or other things can help with your memory and cognition?

[50:39] Dr. Barata: It can help in terms of staying focused, staying engaged, doing specific movements, and repeating instructions. And it helps patients and all of us stay engaged and focused on activities.

[51:01] Moderator: Can we reverse the psychological effects fully?

[51:08] Dr. Barata: There are ways to reverse psychological effects, such as being in touch with social workers, psychologists, and others involved in transplant and CAR T-cell therapy programs.

We know from studies that physical exercise improves mood, supports physical activity, and promotes the release of pleasure hormones. So, there are strategies to improve mood and psychological well-being.

If someone is struggling with psychological issues, please reach out to your team because there are resources at the cancer center or even online resources.

BMT InfoNet has several resources that can also help to deal with psychological symptoms, and modifying and addressing psychological symptoms is going to have a direct impact on cognitive outcomes.

[52:11] Moderator: This person wants to know if curcumin has any effects on cognitive health.

Note: Dr. Barata misunderstood the question and addressed whether a tumor, not curcumin, has an effect on cognitive function.

[52:30] Dr. Barata: The tumor itself can cause inflammation. So, there are several variables that might affect cognitive outcomes, such as whether the disease is directly associated with the brain.

The tumor itself also causes inflammation, which has direct implications for the brain.

It depends on the disease, how it directly impacts the brain (e.g., whether there are metastases), the stage of the disease, whether it is causing inflammation that affects the brain, and the treatment the physicians are using to treat the disease and the inflammation it causes.

[53:12] Moderator: Does pregabalin or gabapentin affect your cognitive functions as well?

[53:27] Dr. Barata: Medications for pain. I guess that this person might be taking this for pain or neuropathy in multiple myeloma.

Sometimes it's important to know why this medication is prescribed, but gabapentin has some specific side effects that might be affecting cognitive issues in terms of being slower. I don't know the specifics of this medication, so I encourage this person to reach out to their healthcare provider.

We know that there are medications for pain or for treating neurological issues that might affect cognitive outcomes. But if someone is concerned about this, I encourage them to reach out to their team, because it may be possible to adjust the dosage or switch to another medication.

I would encourage everyone to reach out and talk about this with their providers because these medications might have side effects that can interfere with patients' quality of life and daily functioning.

[54:34] Moderator: Can you explain more about exercise and how it affects and helps you?

[54:48] Dr. Barata: Exercise is effective in several ways. It keeps the body active. It releases hormones associated with pleasure, which help the body stay active and engaged in physical activity.

Sometimes exercising helps us socialize and connect with others, not only socially but also mentally and cognitively, by engaging in conversations and feeling connected with others, and by increasing self-efficacy, which helps facilitate engagement with other tasks and increase the challenges associated with these tasks. So, exercise is also great for cognitive outcomes.

[55:44] Moderator: All right, doctor. That was our last and final question. Do you have any other comments before we wrap up?

[55:51] Dr. Barata: I want to thank everyone because all these questions were great. I really enjoyed taking part in this presentation and being in touch with all of you. So, thank you all.

[56:07] Moderator: On behalf of BMT InfoNet and our partners, thank you, Dr. Barata, for your helpful and important presentation. I truly loved it myself.

And thank you, the audience, for your excellent questions. Thank you, and have a great day, everyone.