06+Chemo+Brain

=toc [|Wikipedia about Chemo brain]=

Although the causes and existence of post-chemotherapy cognitive impairment have been a subject of debate, recent studies have confirmed that post-chemotherapy cognitive impairment is a real, measurable side effect of chemotherapy that appears in some patients.[|[2]] While any cancer patient may experience temporary cognitive impairment due to stress, fatigue, and depression, the long-term symptoms of PCCI are almost exclusively seen in patients treated for [|breast cancer], [|ovarian cancer], [|prostate cancer], and other cancers of the reproductive system.[|[3]] PCCI is clinically important due to the large number of women who survive breast cancer, more aggressive [|dosing] of chemotherapeutic agents, and the use of chemotherapy as an adjuvant to other forms of treatment.[|[4]] In some patients, fear of PCCI can impact treatment decisions. The magnitude of chemotherapy-related cognitive changes and their impact on the [|activities of daily living] are uncertain.[|[5]]
 * Post-chemotherapy cognitive impairment (PCCI)** (also known as **chemotherapy-induced cognitive dysfunction**, **chemo brain** or **chemo fog**) describes the [|cognitive] impairment that can result from [|chemotherapy] treatment. Approximately 20-30% of people who undergo chemotherapy experience some level of post-chemotherapy cognitive impairment. The phenomenon first came to light because of the large number of breast cancer survivors who complained of changes in memory, fluency, and other cognitive abilities that impeded their ability to function as they had pre-chemotherapy.[|[1]]


 * ==Contents==


 * [|1 Incidence]
 * [|2 Symptoms]
 * [|3 Cause]
 * [|4 Treatment]
 * [|5 Research]
 * [|6 Prognosis]
 * [|7 History]
 * [|8 See also]
 * [|9 Footnotes]
 * [|10 External links] ||

Incidence
PCCI affects a subset of [|cancer survivors],[|[5]] though the overall [|epidemiology] and [|prevalence] is not well known and may depend on many factors.[|[6]] It generally affects about 10-40% of breast cancer patients, with higher rates among pre-menopausal women and patients who receive high-dose chemotherapy.[|[3]]

Sym ptoms
The systems of the body most affected by chemotherapy drugs include [|visual] and [|semantic memory], [|attention] and [|motor coordination].[|[7]] These effects can impair a chemotherapy patient's ability to understand and make decisions regarding treatment, perform in [|school] or [|employment] and can reduce [|quality of life].[|[7]] Survivors often report difficulty multitasking, comprehending what they've just read, following the thread of a conversation, and retrieving words [|[8]] [|Breast cancer] survivors who were treated with chemotherapy have to work harder to perform tasks than survivors whose treatment was surgical. A year after treatment the brains of cancer survivors treated with chemotherapy had physically shrunk while those of people not treated with chemotherapy had not .[|[9]] Post-chemotherapy cognitive impairment comes as a surprise to many cancer survivors. Often, survivors think their lives will return to normal when the cancer is gone, only to find that the lingering effects of post-chemotherapy cognitive impairment impede their efforts. Working, connecting with loved ones, carrying out day-to-day tasks—all can be very challenging for an impaired brain. Although post-chemotherapy cognitive impairment appears to be temporary, it can be quite long-lived, with some cases lasting 10 years or more.[|[10]]

Cause
The details of PCCI's causes and boundaries are not well known.[|[4]] Two major theories have been advanced:[|[3]] the direct effect of chemotherapy drugs on the brain, and the role of hormones in nervous system health. [|Bortezomib] is known to cause [|neuropathy] to the [|sensory] and [|peripheral nervous systems] that is reversible.[|[6]] In most cases there is no known way of reducing the effects of chemotherapeutic agents related to [|taxanes], [|thalidomide] and [|platinum]-based compounds ([|oxaliplatin] is a notable exception to the latter category - though it does cause PCCI its effects can be buffered by infusion of [|calcium] and thought related to PCCI include the ability of the nerves to repair themselves, the ability of cells to excrete compounds, permeability of the [|blood-brain barrier], damage done to [|DNA] including shortening of [|telomeres] and cellular [|oxidative stress].[|[6]] The importance of hormones, particularly estrogen, on cognitive function is underscored by the presence of cognitive impairment in breast cancer patients before chemotherapy is begun, the similarity of the cognitive impairments to several menopausal symptoms, the increased rate of PCCI in pre-menopausal women, and the fact that the symptoms can frequently be reversed by taking estrogen.[|[3]] Other theories suggest [|vascular] injury, [|inflammation], [|autoimmunity], [|anemia] and the presence of the epsilon 4 version of the [|apolipoprotein E] [|gene].[|[7]] PCCI is complex and factors other than the chemotherapeutic agents may impact cognitive functioning. [|Menopause], the biological impact of a surgical procedure with [|anesthesia], [|medications] prescribed in addition to the chemotherapy, [|genetic predisposition], [|hormone therapy], emotional states (including [|anxiety], [|depression] and [|fatigue]), [|comorbid] conditions and [|paraneoplastic syndrome] may all co-occur and act as [|confounding] factors in the study or experience of PCCI.[|[5]]

Treatment
Hypothesized treatment options include the use of [|antioxidants], [|cognitive behavior therapy], [|erythropoietin] and stimulant drugs such as [|methylphenidate], though as the mechanism of PCCI is not well understood the potential treatment options are equally theoretical.[|[7]] [|Modafinil], approved for [|narcolepsy], has been used off-label in trials with people with symptoms of chemobrain. Modafinil is a wakefulness promoting agent that can improve alertness and concentration.[|[11]] A University of Rochester study of 68 subjects had significant results. "We knew from previous studies that modafinil does alleviate problems with memory and attention, and were hoping it would do the same for breast-cancer patients experiencing chemo-brain, which it did," related the study's lead author Sadhna Kohli, Ph.D, a research assistant professor at the University of Rochester's James P. Wilmot Cancer Center.[|[12]] While taking estrogen will frequently reverse the symptoms,[|[3]] this would be dangerous because of the many health risks associated with taking this hormone as a drug.

Research
Research on PCCI is limited, and studies on the subject have often been conflicting in results, in part due to differing means of assessing and defining the phenomenon, which makes comparison and synthesis difficult.[|[5]] Most studies have involved small samples, making generalization difficult, and there has been a focus on younger patients which makes conclusions about the largest group of cancer patients, the [|elderly], difficult to draw.[|[5]] The drug [|doxorubicin] (adriamycin) has been investigated as a PCCI-causing agent due to its production of [|reactive oxygen species].[|[13]] It has been investigated in an [|animal model] with [|mice].[|[13]][|[14]]

Prognosis
While frustrating, the ultimate outcome is very good: symptoms typically disappear in about four years.[|[3]]

History
The symptoms of chemobrain (a phrase coined by June Mari-Gras in 2004 [//[|citation needed]//] ) were recognized by researchers in the 1980s, who typically described it as mild cognitive impairment subsequent to successful cancer treatment.[|[3]] Some authors say that it was identified primarily in [|breast cancer] survivor and [|support groups] as affecting a subset of individuals treated with [|chemotherapy], who attributed it to the effects of the medication taken to treat their cancers.[|[5]]

=[|Introduction to Chemo brain]= of the American Cancer Society

Chemo Brain
//Note that this information is about adults with cancer. To learn more about the effects of cancer treatments in children (including brain problems), see our document called **Childhood Cancer: Late Effects of Cancer Treatment**.// For many years cancer survivors have worried about, joked about, and been frustrated with the mental cloudiness they notice before, during, and after chemotherapy. Even though its exact cause isn't always known, this mental fog is commonly called "chemo brain." Patients have been aware of chemo brain for some time, but only recently have studies been done that could start to explain it. Doctors have known for years that radiation treatment to the brain could cause problems with thinking and memory. More recently, they are finding that chemo is linked to some of the same kinds of problems. (To read more about radiation and its effects, see our information //Understanding Radiation Therapy: A Guide for Patients and Families//.) Research has begun to show that some cancer drugs can, indeed, cause certain kinds of changes in the brain. But it is also showing that chemo is not the only thing that can cause problems with thinking and memory for people with cancer. Though the brain usually recovers over time, the sometimes vague yet distressing mental changes cancer patients notice are real, not imagined. They may last a short time, or they may go on for years. These changes can make people unable to go back to their school, work, or social activities, or make it so that it takes a lot of mental effort to do so. They affect everyday life for many people, and more research is needed to help prevent and cope with them.

What is chemo brain?
Here are just a few examples of what patients call chemo brain: Doctors and researchers call chemo brain "mild cognitive impairment." Most define it as being unable to remember certain things and having trouble finishing tasks or learning new skills. But some doctors call it chemo brain only if it doesn't go away or get better over time. How long it lasts is a major factor in how much it affects a person's life. For most people chemo brain effects happen quickly and only last a short time, while others have long-term mental changes. Usually the changes that patients notice are very subtle, and others around them may not even notice any changes at all. Still, the people who are having problems are well aware of the differences in their thinking. Many people do not tell their cancer care team about this problem until it affects their everyday life. For the person who has lost some brain function, even short-term problems with thinking and memory can be scary. Some people may have trouble remembering simple things, like closing doors or turning off lights. Others may notice that their brain doesn't work as quickly as it used to. These kinds of brain problems can cause trouble at work and at home. People who notice problems with their thinking may feel even more upset if their doctors blame it on aging or act like it's nothing to worry about. It is distressing to wonder if you will ever be able to do your job again, or if you will get lost on the way to a place you've been to dozens of times.
 * Forgetting things that they usually have no trouble recalling -- memory lapses
 * Trouble concentrating -- they can't focus on what they're doing, may "space out"
 * Trouble remembering details like names, dates, and sometimes larger events
 * Trouble multi-tasking, like answering the phone while cooking, without losing track of one of them -- less ability to do more than one thing at a time
 * Taking longer to finish things -- disorganized, slower thinking and processing
 * Trouble remembering common words -- unable to find the right words to finish a sentence

Chemo brain is hard to study.
Clearly, we need to know more about chemo brain. But there are issues that make it hard to study. For instance, researchers sometimes use different tests to measure the problems with thinking and memory, so the results may not compare well with each other. Some people report changes that are so mild that their brain tests look normal and doctors don't have a good way to measure the changes. One study noted that changes like this are reported by people with cancer who didn't get chemo. This may mean the tests in the study weren't sensitive enough to pick up smaller changes. It also suggests that something other than chemo may have caused the problems. Still, chemo is the cause of major brain problems in some people with cancer. Many of these people have brain function problems that are directly related to cancer or its treatment, and most of these problems do show up on testing. There are also differences in when certain kinds of brain problems happen. Some researchers have tested brain function a few weeks after treatment, others months or even years later. If the problem only lasts a few weeks with no long-term changes, late testing can miss it. If the changes last more than a year but the testing stops after 6 months, no one knows how long they last. Beyond the chemo brain symptoms that start during and just after treatment, there are some cases where brain symptoms start and even get worse after treatment is over. Many cancer treatments, including chemo and radiation, can cause short-term, long-term, and delayed problems. Another timing problem in studying chemo brain is that most studies haven't tested the patients before treatment to compare to results after treatment. In studies that tested before treatment, some people were seen to have brain function problems before treatment was even started. So it's possible that the cancer itself causes some of the problems, or that some other related problem caused brain function to decline. Studies are needed that test people before the treatment and then follow up to look for changes over time. Differences in how chemo brain is defined can also make it hard to get a handle on how often it happens. There is a wide range of estimates of how many people get chemo brain. One expert noted that, among people who get chemo, between 15% and 70% have brain symptoms. Another expert put the upper limit of the range at 50%. So we only know that the risk of chemo brain (for people who get chemo) can be higher than 1 out of 2 or as low as 1 in 6. That may not take into account people with brain or thinking problems that may be due to their cancer or other causes. When it starts, how long it lasts, and how much trouble it causes can vary a lot. So the term "chemo brain" is not completely accurate, Still, it is what most people call it right now.

What causes chemo brain?
Studies suggest that there may be more than one cause of chemo brain, especially for the short-term symptoms. Some people with cancer have very real brain problems even though they have not had chemo. Still others notice problems during hormone treatments. Along with chemo, there are many different problems that can worsen brain function. For example, brain problems could be caused or worsened by any one or any combination of the following factors: Most of these cause short-term problems, and get better as the underlying problem is treated or goes away. A few factors, such as depression, can cause long-lasting brain problems unless the cause is treated. So far, there are no known ways to prevent chemo brain while getting cancer treatment. For some people, treating their cancer will mean trouble with thinking, memory, planning, and word finding.
 * The cancer itself
 * Other drugs used as part of treatment (such as anti-nausea or pain medicines)
 * Patient age
 * Stress
 * Low blood counts
 * Sleep problems
 * Infection
 * Depression
 * Tiredness (fatigue)
 * Hormone changes or hormone treatments
 * Anxiety or other emotional distress

Studies of brain problems related to cancer and its treatment
Imaging tests have shown that in some patients, the parts of the brain that deal with memory, planning, putting thoughts into action, monitoring thought processes and behavior, and inhibition are smaller after chemotherapy. In some studies, these problems were more common in those who got high-dose chemo (such as chemo used for stem cell or bone marrow transplant). But a recent study of people who were tested before stem cell transplant noted that some problems had started before the transplant, and that memory greatly improved over the next 18 months. At that time some still had trouble with slower reaction times and fine muscle coordination, but other functions were better. In another series of studies, brain problems that were present 2 years after treatment were much better 4 years after treatment. Pictures of the brain have shown lower resting brain activity of breast cancer survivors treated with chemo when compared with those who were not treated with chemo. These changes were still seen on scans of some women 5 to 10 years after treatment stopped. But during memory testing, these women had to call on and use larger areas of their brains than women who had not gotten chemo. In people with brain problems, tests of memory usually show the person is slow to learn new things, and they take longer to recall what they know. Response or reaction times slow down; attention and concentration often suffer. Most often, tests find that the person with chemo brain has more trouble in using recalled information (executive function), and in using language. What is known for sure is that brain slowdown is a real problem that affects both men and women. Most of these people will notice that the problems get better over time. But others will have to learn ways to deal with chemo brain that doesn't go away.

Day-to-day coping
Experts have been studying memory for a long time. There are many resources that might help you sharpen your mental abilities and manage the problems that may come with chemo brain. Some things that you can do are:
 * Use a detailed daily planner. Keeping everything in one place makes it easier to find the reminders you may need. Serious planner users keep track of their appointments and schedules, "to do" lists, important dates, phone numbers and addresses, meeting notes, and even movies they'd like to see or books they'd like to read.
 * Exercise your brain. Take a class, do word puzzles, or learn a new language.
 * Get enough rest and sleep.
 * Exercise your body. Regular physical activity is not only good for your body, but also improves your mood, makes you feel more alert, and decreases tiredness (fatigue).
 * Eat your veggies. Studies have shown that eating more vegetables is linked to keeping brain power as people age.
 * Set up and follow routines. Pick a certain place for commonly lost objects and put them there each time. Try to keep the same daily schedule.
 * Don't try to multi-task. Focus on one thing at a time.
 * Ask for help when you need it. Friends and loved ones can help with daily tasks to cut down on distractions and help you save mental energy.
 * Track your memory problems. Keep a diary of when you notice problems and the events that are going on at the time. (You might track this in your planner.) Medicines taken, time of day, and the situation you are in may help you figure out what affects your memory. Keeping track of when the problems are most noticeable can also help you prepare. You'll know to avoid planning important conversations or appointments during those times.
 * Write down questions to talk over with your doctor about the problems you have. Ask what may be causing them, and find out if there is anything the doctor can offer to help you.
 * If your memory and thinking problems keep causing trouble in your daily life, ask your doctor if you might be helped by a neuropsychologist. These professionals can test brain function and possibly recommend ways to help you deal better with the problems. You'll want to find out what your insurance will cover before you start.
 * Try not to focus so much on how much these symptoms bother you. Accepting the problem will help you deal with it. As many patients have noted, being able to laugh about things you can't control can help you cope. And remember, you probably notice your problems much more than others do. Sometimes we all have to laugh about forgetting to take the grocery list with us to the store.

Telling others
Another thing you can do to better manage chemo brain is tell family, friends, and your healthcare team about it. Let them know what you are going through. You may feel relieved once you tell people about the problems you sometimes have with your memory or thinking. You are not stupid or crazy -- you just have a side effect that you have to learn to manage. Even though this is not a change that is easy to see, like hair loss or skin changes, your family and friends may have noticed some things and may even have some helpful suggestions. For instance, your partner may notice that when you are rushed, you have more trouble finding things. Tell your loved ones what they can do to help. Their support and understanding can help you relax and make it easier for you to focus and process information. Many large hospitals and cancer centers have neurologists, psychoneurologists, and psychologists who are experts at testing brain function, including the symptoms of chemo brain. Testing can help specialists find the extent of your symptoms and then suggest the best mental exercises for you. You may want to ask to be referred to one of these specialists who can help you learn the scope of your problem and work with you on ways to manage it.

Can chemo brain be prevented?
The causes of chemo brain are still being studied, and at this time there is no known way to prevent it. It seems to happen more often with high doses of chemo, and is more likely if radiation treatments to the brain are also used. But because chemo brain is usually mild and most often goes away over time, chemo that is proven to work against the cancer should not be changed to try to prevent this side effect.

What is being done about chemo brain?
Now that chemo brain has been linked to cancer and its treatment, studies are being done to learn more about it. Some studies are looking to find out which chemo drugs and other treatments are more closely linked to chemo brain. Researchers are also looking at possible ways to prevent chemo brain. For instance, some drugs are being looked at as possible ways to protect the brain, but these have yet to be tested in humans. Researchers are studying other aspects of cancer treatment that may lead to long-term mental changes, too. For example, they are looking at the types and doses of chemo the patients had, anemia, other cancer-related symptoms (like tiredness), and genetic differences among people to see if these factors are linked to a higher risk of chemo brain. Doctors are also studying ways to help survivors who are still having trouble thinking.

Future directions
Looking at how chemo brain happens Recent studies have shown clear evidence of nerve damage from at least some forms of chemotherapy. But studies of the effects of chemo drugs on brain cells are rare. Special imaging tests must be used to help pinpoint areas of increased and decreased activity in the brain. This is a focus of ongoing research. Scientists must find out which nerve cells or brain cells are at risk during cancer treatment in order to develop ways to reduce damage, save brain function, and maintain the quality of life in long-term survivors. So far, early studies in the lab and in animals suggest that certain chemo drugs may harm some nerve cells even after the drug is stopped. But more research is needed to see if this happens in humans, too. There is more concern about chemo brain now because cancer treatment study results have shown better outcomes with the use of more aggressive, high-dose drug schedules. There are also newer targeted drugs that are known to affect certain pathways that are part of nerve cell formation and stem cell function, which is a cause for concern. Learning which nerve cells are affected may help scientists test new drugs for this side effect.

Preventing chemo brain
Cancer experts are looking into treatment options that may protect the brain from chemo side effects. Targeted drugs that focus on the cancer cells and spare normal cells, such as brain and nerve cells are being studied.

Treating chemo brain
Researchers are looking at medicines that are now used for problems like depression, attention-deficit hyperactivity disorder (ADHD), Alzheimer disease, and dementia. These might serve as possible treatments for chemo brain, but more testing is needed.

Looking for other links to chemo brain
Genetic differences that may make some people more likely to have symptoms of chemo brain are being explored. One particular gene, called APOE, is being looked at closely. Research has shown that a version of this gene, called E4, is linked to Alzheimer disease. When E4 is present, there is an increased chance of thinking problems after traumatic brain injury, too. Studies are being done to find out if people who have the E4 gene and get chemotherapy have a higher risk of developing long-term chemo brain. Recognizing that chemo brain can be a treatment side effect was the first step. Doctors and researchers are now trying to measure it -- how exactly does it affect patients' brains and cause changes? This important information can help them find ways to not only treat chemo brain, but in the future, help to prevent it.