How to Manage Chemobrain


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Cognitive effects of cancer and cancer treatment -- also known as chemobrain -- are widely recognized. Dr. Fremonta Meyer from Dana-Farber Cancer Institute, talks about what chemobrain is, research into its effects, and how to manage and/or treat it.

For more information, watch our YouTube video on chemobrain here:

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  • Lost wages, credit card late fees, higher car insurance premiums. “My condition is as real as the cost has been.”
  • This was a study done in 2007 in about 600 patients who were being treated with chemotherapy and radiation for solid tumors. Patients self-reported any problems with memory and concentration. Women had more symptoms than men during treatment. About ½ of patients had problems at baseline, before any treatment. This went up to 67% during treatment, and remained at 50-60% 6 months after treatment. The graphs show that chemo was significantly more likely to cause problems than radiation. They also show that for most patients, the problems were fairly mild (0=no problem; 10=worst problem you could imagine). But they suggest that people are still having some trouble 6 months after chemotherapy ends.
  • Basal ganglia- control the decision of which of several possible behaviors to execute at a given time
  • This was a study of 60 y/o twins who were raised together. Twin A had breast cancer and was 2 years out from chemotherapy; twin B did not have cancer. They put both twins in a functional MRI scanner. They tested working memory by asking the twins to listen to a string of letters presented once every 3 seconds. The twins had to press a button if the letter was a match with a designated target (e.g. “F”) or if it was the same as the letter presented 3 back in the sequence (e.g. “C”). The results were that both twins were equally accurate at the task. But twin A (top) had to activate a much larger area of the brain than twin B did. So, this may translate into twin A experiencing the task as more difficult.
  • And anecdotally, breast cancer survivors complain about this a lot.
  • Don ’t have OS or PS like oncologists!!
  • Most objective to least objective ; most expensive to least expensive
  • Unlikely to be stress of dx, given findings in stage 0 patients vs stage I-III pts. RF: higher levels of proinflammatory cytokines may be correlated with both cancer and MCI/AlzD, or polymorphisms in DNA repair genes
  • In this study (published in early 2011) researchers wanted to see if the chemo drugs that cross the BBB were more likely to interfere with growth of neurons than the chemo drugs that don ’t cross the BBB. They took mice and gave 1 group saline and the other group chemotherapy. On the 2 nd day, they injected all the mice with a tracer chemical that binds to neurons. On the 3 rd day, they sacrificed the mice and isolated their brains. Then after 5 days of incubation they examined the dentate gyrus. What they found was that all of the 4 chemotherapy drugs, even the 2 that don’t cross the BBB, caused reduced growth of neurons. The reductions ranged from 15% to 36%. There was no cell death – only a slowing in growth.
  • Growth factors are proteins that stimulate cells to grow and mature. Some of you probably took Neupogen during chemotherapy (G-CSF). This is a growth factor that stimulates white blood cells to grow. They are many others which make other cells (including neurons) grow.
  • b/c Self-reported cognitive dysfunction correlates with these sx – NOT objective cognitive findings
  • In a study published on Jan. 31, 2011, in The Proceedings of the National Academy of Sciences, researchers randomly assigned 120 healthy but sedentary men and women (average age mid-60s) to one of two exercise groups. One group walked around a track three times a week, building up to 40 minutes at a stretch; the other did a variety of less aerobic exercises, including yoga and resistance training with bands. After a year, brain scans showed that among the walkers, the hippocampus had increased in volume by about 2 percent on average; in the others, it had declined by about 1.4 percent. Since such a decline is normal in older adults, “a 2 percent increase is fairly significant,” said the lead author, Kirk Erickson, a psychologist at the University of Pittsburgh. Both groups also improved on a test of spatial memory, but the walkers improved more.
  • I think it ’s important to mention here that there is a stigma associated with seeking help for emotional problems. Many of you may never have done this before cancer. But I think at the same time when you’re in this situation it’s even more important to challenge yourself on that stigma and take advantage of any resources that may be able to help you.
  • I ’m a psychiatrist, so I can’t get through a talk without focusing on some of the areas
  • Here, physical reactions can be replaced with “cognitive side effects/chemobrain”
  • Brain plasticity refers to the brain ’s ability to change at any age (not just in childhood). Gray matter can grow or shrink. Neural connections can be forged, or severed. Forgetting a name reflects weakened wiring. Learning a new dance step strengthens a set of wiring.
  • Growing out of the emerging recognition that brain function is far more distributed than localized, with each neuron broadly connected in networks, it uses a single sensor for each hemisphere (placed midway between the top of the ear and the crown of the head), and simultaneously analyzes the activity at eight clusters of frequencies ( “time-frequency envelopes”) in each hemisphere. The software does not reward the brain for movement toward a “normal” or “desired” pattern, but simply provides information to the brain—in the form of very brief subliminal interruptions in music the subject is hearing—whenever the brain shows signs of turbulence (indicated by phase state changes) in one or more of the 16 time-frequency envelopes. These brief interruptions trigger the orienting response in the brain, which—as a complex adaptive system—is able to self-organize in a way that avoids continued turbulence and moves to a more optimal dynamical pattern of flexibility and resilience. Interestingly, the concept of “turbulence,” as used in this software, is a mathematical concept, not an experiential one, so the client undergoing this form of neurofeedback is generally unaware of the brain activity triggering the feedback and the brain’s response.
  • How to Manage Chemobrain

    1. 1. Cognitive Changes after Breast Cancer and its Treatment Fremonta Meyer, MD Department of Psychosocial Oncology and Palliative Care Dana-Farber Cancer Institute June 6, 2012
    2. 2. Outline Impact Why focus on breast cancer? Research findings Interventions
    3. 3. What symptoms are you experiencing?
    4. 4. So… Is it real? What causes it? What can be done about it?
    5. 5. Patient Experiences “I have been so lost [while driving], I just pull over, and break down and start crying. Because it’s places I’ve been before and I know where I am going…” “I couldn’t remember if I looked at a stoplight. I felt like it was putting myself at risk.” “What I have to do sometimes is have my son come over and pay my bills.”* * Boykoff et al, J Cancer Surviv, 2009
    6. 6. Impact on Quality of Life Distress due to lack of acknowledgment by medical community Mixed reactions from family and friends Decline in job performance Avoidance of social occasions Depression and anxiety * Boykoff et al, J Cancer Surviv, 2009
    7. 7. Chemobrain can affect many areas of cognitive function Memory Attention/concentration Information processing speed Executive function  Initiation  Planning  Organization  Multi-tasking  Response inhibition
    8. 8. Research shows that the majority of patients on chemotherapy experience cognitive side effects 67% of patients reported experiencing memory and concentration problems during chemotherapy These problems were still present 6 months after completing chemotherapy Memory Concentration *Kohli et al, J Oncol Practice, 2007
    9. 9. For most people, chemobrain gradually disappears over time 17-34% of people continue to have problems after the end of chemotherapy Some neuroimaging studies show improvement/resolution of regional brain volume differences as of 3 years post- chemotherapy *Inagaki et al, Cancer, 2007
    10. 10. Chemobrain leads to dysfunction of frontal-subcortical brain networks
    11. 11. Chemobrain is not the same as dementia Chemobrain is not a progressive condition Chemobrain does not increase risk for Alzheimer’s disease The cognitive findings in Alzheimer’s disease are different  In Alzheimer’s, memory cues don’t help  In chemobrain, memory cues help
    12. 12. *Ferguson et al, JCO, 2007
    13. 13. Why do we study breast cancer? Common cancer with largest population of survivors (23%; 2.6 million) Limited direct effects of cancer on brain other than chemotherapy Population allows chemotherapy vs non- chemotherapy study designs
    14. 14. Why don’t more oncologists study this? Oncology research tends to focus on clearly defined outcomes or “endpoints”  Overall survival (OS)  Progression-free survival (PS) What’s the “endpoint” for chemobrain?
    15. 15. Endpoints for chemobrain are controversial.  Functional neuroimaging findings (fMRI)  Neuropsychological tests  May not reflect “real life”  Self-reported cognitive problems  May have other causes  But, interestingly, seems to be most similar to fMRI results
    16. 16. Empathy for your oncologist and other physicians… It’s important to understand where your oncologist is coming from…  The research on this topic is very confusing  There aren’t yet any FDA approved treatments for chemobrain  This makes it hard for them to know what to recommend!
    17. 17. Problems with the Older Research Cross-sectional studies  Looking only at people who already completed cancer treatment Prospective studies without matched control groups  Looking only at people who had cancer and received chemotherapy Not enough patients Multiple chemotherapy regimens Not controlling for hormonal therapies Not controlling for patients getting better at neuropsychological tests because they have practiced them (rather than their chemobrain actually improving) Excluding people with depression, anxiety, sleep problems
    18. 18. Summary of the better-quality research using neuropsychological testing 8 prospective longitudinal studies with matched control +/- healthy control group*  Acute declines in motor skills, processing speed, verbal/visual memory which improved over time  Chemotherapy may have specific negative effect on verbal fluency  Patients exposed to chemotherapy plus tamoxifen did worse at later timepoints than pts exposed to chemotherapy alone  But: 3 studies did not show any cognitive impairment with standard-dose chemotherapy *Quesnel 2009, Schagen 2009, Tager 2010, Bender 2006, Collins 2009, Jenkins 2006, Mehlsen 2009, Ahles 2010
    19. 19. How would you design astudy, from your perspective as a cancer survivor?
    20. 20. Added Observations Some people with breast cancer (11-33%) have cognitive problems prior to receiving any chemotherapy at all*  Anxiety  Anesthesia from surgeries  Something that the tumor directly causes – “paraneoplastic” *Ahles et al, Breast Cancer Res Treat, 2008
    21. 21. The dentate gyrus of the hippocampus isinvolved in the formation of new memories
    22. 22. A Close-Up of the Dentate Gyrus
    23. 23. What chemotherapy regimens do most women receive for breast cancer? “AC” then “T”:  A=adriamycin (doxorubicin)  C=cyclophosphamide (Cytoxan)  T=docetaxel (Taxotere)
    24. 24. What is the blood-brain barrier (BBB)? Microscopic objects (e.g. bacteria) can’t get in. Neither can hydrophilic molecules. But it doesn’t keep everything out…
    25. 25.  Cyclophosphamide (cytoxan) and 5- fluorouracil (often used in treatment for colon cancer) can cross the BBB. Doxorubicin and paclitaxel do not directly cross the BBB.
    26. 26. In mice, chemotherapy agents appear to result in reduced cell growth in the dentate gyrus of the hippocampus *Janelsins et al, Cancer Investigation, 2010
    27. 27. Take-Home Points Even chemotherapies that do not cross the BBB (such as doxorubicin and doxetaxel/paclitaxel) may result in decreased neurogenesis (growth of neurons) Growth factors may result in increased survival of neural cells  IGF-1, BDNF, VEGF, FGF So, if we can confirm these findings in humans, we could speculate that growth factors may help future patients…. BUT… What could be the problem with giving growth factors? *Joshi et al, Neuroscience, 2010
    28. 28. “Seed” “Soil” “Pesticide”
    29. 29. Cancer and Chemotherapy… Leads to increased production of inflammatory chemicals called cytokines e.g. TNF (tumor necrosis factor) Higher levels may predict worse cognitive function after chemotherapy for breast cancer* Some women had genetic differences in the TNF gene that made them less likely to develop problems What are these differences? *Ganz, et al, abstract at ASCO, 2011
    30. 30. Single Nucleotide Polymorphisms (SNPs) Variations in sequences of DNA A single allele is different Make us differentially susceptible to (or protected from!) all kinds of diseases Examples:  TNF  BDNF (brain-derived neurotropic factor)  Apolipoprotein (ApoE4=more prone to Alzheimer’s disease) These SNPs may make some people unable to repair the DNA damage that causes cognitive problems
    31. 31. Hormonal therapy for breast cancer may also have a negative effect on cognition High levels of estrogen increase verbal memory, verbal fluency and fine motor skills Surgically induced or abrupt menopause  Acute decline in verbal memory It’s unclear that hormone replacement therapy truly protects against dementia Tamoxifen and aromatase inhibitors (eg Aromasin, Arimidex, Femara) may have an anti-estrogen role in some brain areas related to cognitive function  Effects are not widespread or severe  Primarily seen in verbal memory and processing speed
    32. 32. Chemobrain is associated with several common, treatable problems Sleep disturbance Fatigue Depression Anxiety
    33. 33. What can be done?
    34. 34. Medications-1 Stimulants  methylphenidate (Ritalin, Concerta, Focalin), dextroamphetamine (Adderall)  Despite negative study*, they are sometimes effective in clinical practice Modafinil (Provigil)*  Improved attention and memory in a group of breast cancer survivors with fatigue *Mar Fan et al, Support Care Cancer, 2008 *Kohli et al, Cancer, 2009
    35. 35. Medications-2 Antidepressants  Celexa (citalopram), Zoloft (sertraline), Lexapro (escitalopram), Prozac (fluoxetine), Paxil (paroxetine)  Effexor (venlafaxine), Cymbalta (duloxetine)  Wellbutrin (bupropion)  Remeron (mirtazapine) Anxiolytics  lorazepam (Ativan), clonazepam (Klonopin), alprazolam (Xanax), diazepam (Valium)  Use with caution Sleep medications  zolpidem (Ambien), eszopiclone (Lunesta), trazodone (desyrel)  Use with caution
    36. 36. SSRIs (e.g. citalopram, fluoxetine, sertraline)increase levels of BDNF, increase neurogenesis,and increase branching of dendritic connections.
    37. 37. Other Activities Regular aerobic exercise  May improve neural proliferation in the dentate gyrus!  In a review of many studies, this was the only factor associated with lowering your risk of dementia Social connections Good nutrition  e.g. fish w/omega 3’s, antioxidants, flavanols
    38. 38. First Step: Get Help! If you’re more than 6 months out from chemotherapy and you are having difficulty functioning in your daily life (with work, school, relationships) due to chemobrain… Ask your oncologist for a referral to a neuropsychologist. A neurologist can be helpful if you have a family history of dementia, or if you have other neurological symptoms such as persistent neuropathy, headaches, weakness/numbness in a body part, etc. If you have any sleep problems, fatigue, depression, or anxiety:  Consider seeing a psychiatrist  Also consider seeing a sleep medicine physician (who can decide if a sleep study is needed). Finally, make sure your PCP is in the loop.
    39. 39. Sleep Apnea… Weight gain after breast cancer treatment puts people at higher risk Masks are more comfortable than they used to be Don’t give up!! Start with a few hours a night and work up gradually
    40. 40. Cognitive Behavioral Therapy Usually delivered by a psychologist, psychiatrist, or social worker Research shows it’s very effective for depression and anxiety Doesn’t necessarily change your chemobrain, but changes your relationship with your chemobrain Corrects negative “automatic thoughts” and distortions
    41. 41. Cognitive Behavioral Therapy Triad/Quartet
    42. 42. Filtering: We take the negative details and magnify them while filtering out all positive aspects of a situation. For instance, a person may pick out a single, unpleasant detail and dwell on it exclusively so that their vision of reality becomes darkened or distorted.“Black and White” Thinking: In polarized thinking, things are either “black-or-white.” We have to be perfect or we’re a failure — there is no middle ground. You place people or situations in “either/or” categories, with no shades of gray or allowing for the complexity of most people and situations. If your performance falls short of perfect, you see yourself as a total failure.Overgeneralization: In this cognitive distortion, we come to a general conclusion based on a single incident or a single piece of evidence. If something bad happens only once, we expect it to happen over and over again. A person may see a single, unpleasant event as part of a never-ending pattern of defeat.Jumping to Conclusions: Without individuals saying so, we know what they are feeling and why they act the way they do. In particular, we are able to determine how people are feeling toward us. For example, a person may conclude that someone is reacting negatively toward them but doesn’t actually bother to find out if they are correct. Another example is a person may anticipate that things will turn out badly, and will feel convinced that their prediction is already an established fact.
    43. 43. Catastrophizing: We expect disaster to strike, no matter what. This is also referred to as “magnifying or minimizing.” We hear about a problem and use what if questions (e.g., “What if tragedy strikes?” “What if it happens to me?”). For example, a person might exaggerate the importance of insignificant events (such as their mistake, or someone else’s achievement). Or they may inappropriately shrink the magnitude of significant events until they appear tiny (for example, a person’s own desirable qualities or someone else’s imperfections)Personalization: Personalization is a distortion where a person believes that everything others do or say is some kind of direct, personal reaction to the person. We also compare ourselves to others trying to determine who is smarter, better looking, etc. A person engaging in personalization may also see themselves as the cause of some unhealthy external event that they were not responsible for. For example, “We were late to the dinner party and caused the hostess to overcook the meal. If I had only pushed my husband to leave on time, this wouldn’t have happened.”Control Fallacies: If we feel externally controlled, we see ourselves as helpless a victim of fate. For example, “I can’t help it if the quality of the work is poor, my boss demanded I work overtime on it.” The fallacy of internal control has us assuming responsibility for the pain and happiness of everyone around us. For example, “Why aren’t you happy? Is it because of something I did?”Fallacy of Fairness: We feel resentful because we think we know what is fair, but other people won’t agree with us. As our parents tell us, “Life is always fair,” and people who go through life applying a measuring ruler against every situation judging its “fairness” will often feel badly and negative because of it.
    44. 44. Shoulds: We have a list of ironclad rules about how others and we should behave. People who break the rules make us angry, and we feel guilty when we violate these rules. A person may often believe they are trying to motivate themselves with shoulds and shouldn’ts, as if they have to be punished before they can do anything. For example, “I really should exercise. I shouldn’t be so lazy.” Musts and oughts are also offenders. The emotional consequence is guilt. When a person directs should statements toward others, they often feel anger, frustration and resentment.Emotional Reasoning: We believe that what we feel must be true automatically. If we feel stupid and boring, then we must be stupid and boring. You assume that your unhealthy emotions reflect he way things really are — “I feel it, therefore it must be true.”
    45. 45. Naming Emotions Anxiety= signal of an emotion that lies underneath Primary emotions (like primary colors!)  Sadness  Fear  Anger  Guilt  Shame  Envy  Jealousy Naming the emotion can reduce the anxiety
    46. 46. Behavioral Approaches Behavioral activation Systematic desensitization  Gradually exposing yourself to feared situations over time
    47. 47. Cognitive rehabilitation helps many patients It’s done by a speech-language pathologist  This is often covered by insurance – specifically, your physical/occupational therapy benefit Exercises to retrain your brain Tracking and understanding what causes cognitive worsening  e.g. fatigue Coping strategies  PDAs; 1 notebook w/3 sections; Note taking Stress relief strategies  Diaphragmatic breathing; muscle relaxation; guided imagery
    48. 48. The idea behind cognitive rehabilitation is to compensate for the deficits by learning to work around them “But… I want my backhand to come back!!”
    49. 49. Newest developments are trying to take advantage of brain plasticity to restore function POSIT brain science program (  40-hour training program  Effective for age-related cognitive decline and mild cognitive impairment  It’s being studied in chemobrain by Janelle Vardy at the University of Sydney  Study results not yet available
    50. 50. EEG Biofeedback
    51. 51. Preliminary Study of EEG Biofeedback Preliminary data from Alvarez et al (we are submitting to journals presently): 23 breast cancer survivors showed marked improvements in self-reported cognitive function, sleep, and fatigue after 20 sessions of neurofeedback over 10 weeks More study with neuropsychological tests is needed.
    52. 52. In order to have chemobrain, you have to be alive