Side Effects of Treatment: "Chemo Brain"

Doctors from MDACC and Univ of Rochester explain the cause, signs and symptoms of "chemo brain"

Medically reviewed by Dr. C.H. Weaver M.D. Medical editor-updated 9/20/2018

This often-unexpected side effect of cancer treatment leaves many patients experiencing debilitating cognitive effects after chemotherapy. Luckily, research and awareness are catching up.

Ten years ago Sharon Palmatory’s trouble remembering names and numbers after chemotherapy treatment for breast cancer might have been brushed aside as an insignificant occurrence, considering survival was the primary concern. But today, thanks to early diagnosis and effective treatment, more women survive breast cancer than ever before, and quality-of-life issues like this are increasingly important.

“It’s a definite medical condition,” says Dr. Christina Meyers, PhD, ABPP, professor of neuropsychology in the Department of Neuro-Oncology at M. D. Anderson Cancer Center in Houston, describing what has come to be known as “chemo brain,” a lesser-known side effect of chemotherapy, which can be just as serious as nausea, fatigue, and hair loss. Thankfully, the condition—marked by a reduction in verbal or visual memory, problems with attention and concentration, a reduction in the speed of processing information, and visual or spatial abnormalities—is the subject of several recent studies, as researchers seek clues to the cause and the cure of this foggy mental condition1

“Those involved in long-term follow-up care for survivors are well aware of their patients’ complaints that they cannot mentally function as well after treatment as before,” says Dr. Mark Noble, professor of genetics at the University of Rochester School of Medicine and Dentistry in Rochester, New York. Too many people are affected to ignore the syndrome—and not just breast cancer patients or women. Men experience the foggy mental state associated with chemotherapy, too. As a result, oncologists and nurses now make a better effort to provide patients with information about the possibility of cognitive impairment occurring either during or after active treatment.

Still, many patients are surprised by the debilitating impact of the condition. “I honestly didn’t know this would happen,” says Sharon, 39, of Morgantown, West Virginia. “I was more concerned with fatigue and taking care of my family.” But after her second chemotherapy treatment, she went into a general fog for a week. “I couldn’t multitask,” she says of the way the devastating side effect affected her demanding career as a multimedia designer for government projects. “Losing my train of thought was scary. And I couldn’t manage the household, remember names and numbers, or balance my checkbook.”

Following her fourth treatment, Sharon hit her lowest point, after which improvement started slowly. “I still have a one-track mind, although treatment ended several months ago,” she says. “I always have a pad of paper to write things down.” She laughs that at her age she can’t attribute these lapses to senior moments. “I rely on my husband to remind me of appointments. The exit door to my garage is plastered with notes.”

Recognizing the Condition

Doctors used to think that impaired cognitive ability was related to other side effects of chemotherapy. Anemia, fatigue, depression, and hormonal shifts can all cause memory lapses and concentration difficulties. But treating these conditions didn’t solve the problem for many patients. And assessing the severity was difficult because there was no baseline data of mental function before chemotherapy.2

“We now know that chemo brain is a manifestation of central nervous system toxicity that occurs in many cancer patients on active therapy and may persist for 45 percent of patients after treatment is discontinued,” says Dr. Meyers. Researchers also believe that some people have genes that make cancer more responsive to treatment. This puts normal tissue at risk for changes and makes them more susceptible to mental effects from chemotherapy.

“We know a fair deal about the damage done to the brain by radiation but virtually nothing about the effects of chemotherapy,” says Dr. Noble. “Imaging studies have shown clearly that high doses of chemotherapy result in changes.” What isn’t known yet is which chemotherapy drugs cause problems and how.

What Are the Newest Findings?

Fortunately for breast cancer patients (the type of cancer most frequently studied for cognitive impairment), chemo brain is currently a hot topic in the lab. Researchers are discovering more about how the brain and the nervous system are affected by toxic drugs used in chemotherapy. Still, not everyone is affected, and scientists haven’t ferreted out enough clues to determine who is at risk.

With aggressive treatment the cure rate for Stage I cancers has grown as high as 90 percent, yet not every woman with breast cancer needs chemotherapy, although most get it, says S. David Nathanson, MD, surgical oncologist at Henry Ford Health System in Detroit. That’s significant because up to 25 percent of women who do receive it will be affected by chemo brain—a statistic that complicates the decision about who should get chemo.

Despite advances in brain research during the past decade, the exact mechanisms for cognitive impairment aren’t clearly understood, although it’s recognized that standard chemotherapeutic agents can kill normal brain cells. Dr. Noble’s research is attempting to understand how stem cells function, with the hope of using them to prevent abnormal reactions or to successfully repair damaged tissue.

“If we can’t prevent the damage, can we repair it by stem cell or precursor cell transplantation?” he asks. “It may be possible to use brain cell transplantation to restore normal function, much as bone marrow transplantation is used to restore normal function of the hematopoietic system (organs and tissues involved in the production of blood) following cancer treatment,” he says.

Dr. Noble explains further: “In many ways, a cancer cell can be thought of as the evil sibling of a stem cell. Understanding the features that distinguish cancer cells from normal cells may enable cancer-specific treatments to be developed without negatively affecting quality of life for long-term survivors.” It may also help researchers develop a means of selectively protecting normal cells from damage caused by radiation and chemotherapy.

“The only way to prevent or treat cognitive impairment associated with cancer therapy is to understand why it occurs,” Dr. Noble adds. “One of our concerns is to be able to better understand the reason for different outcomes. Understanding why some people are resistant to these effects will enable us to protect those who are more vulnerable, perhaps by modifying treatment accordingly.”

Two major studies are being conducted at the University of Sydney Cancer Centre in Australia by oncologist Janette Vardy, MD. By studying brain scans and blood tests from breast cancer patients (other research is with colorectal cancer), her team has found that those who never received chemotherapy, although they had breast cancer, had functional MRI scans more like those of healthy control persons—and different from those of patients who had received chemotherapy. “What we don’t know is how those scanned differences will relate to how a person copes in normal life,” Dr. Vardy says.

In tests on the central nervous systems of experimental animals, Dr. Noble’s team has found that during chemotherapy there is a long-lasting reduction in cell division in the hippocampus of the brain, an action believed necessary for normal memory function. “Our work shows that there is damage to the insulation (myelin) that surrounds axons, with eventual loss of the cells that produce the myelin. A lack of myelin could also cause cognitive problems.”

Breakthroughs may also result from research by Jame Abraham, MD, director of the Comprehensive Breast Cancer Program at West Virginia University’s Mary Babb Randolph Cancer Center. His team is one of the first to investigate which specific changes in the brain lead to memory loss. Early research shows differences in the white matter in the front part of the brain in women who had received chemotherapy—differences that correlate with their slower speed in processing information. “Our preliminary findings suggest that chemotherapy may change the brain, and those changes affect the patient’s cognitive skill,” Dr. Abraham says. West Virginia University researchers also concluded that these changes do not appear to be caused by depression or anxiety.3 For those affected, Dr. Abraham’s research regarding direct damage to the brain from chemotherapy brings validation to their claims.

What’s a Patient to Do?

Sharon Palmatory, a patient of Dr. Abraham’s, has suffered typical side effects from her treatment. She explains: “I feel like I’m always two paces behind—always struggling to keep up. When I lose my train of thought, it’s hard to get it back.” The problem was severe enough for her to request a transfer to slower-paced work with less aggressive deadlines. (Dr. Meyers says 14 percent of affected people have to discontinue work altogether.) “I couldn’t predict my reaction to treatment on any given day,” says Sharon. Disorganization and distractibility, when it occurred, affected her ability to perform at her previous level.

Although ongoing research is bringing physicians closer to developing targeted treatments for preventing or treating chemo brain, patients like Sharon are left to cope with various levels of cognitive impairment. Many will recover normal or near-normal levels a year or two after chemotherapy, but quality of life in the interim requires implementing strategies for dealing with the mental haze. “Maintaining function is important,” says Dr. Meyers. Sharon agrees, saying brain function is a “use it or lose it” issue.

In an instructional video provided to patients, Dr. Meyers outlines several types of cognitive impairment that fall under the “chemo brain” label:

  • Reduced memory capability, both verbal and visual (“What’s your name again?”)
  • Lack of focused attention or ability to process information (must read a paragraph several times to get the meaning)
  • Learning new things takes longer (even though you’re still as smart as before)
  • Multitasking is overwhelming (can’t talk on the phone and cook dinner at the same time)
  • Easily distracted (“Why did I come in this room?”)
  • Missing key points in discussion (“Please repeat what you just said”)
  • Inability to find right word in conversations (You can’t just say “duh”)
  • More effort required for usual tasks (daily activities leave you very fatigued)

Learning Adaptive Behaviors

“Although it can be aggravating, having chemo brain is better than the alternative,” reminds Dr. Meyers. After ruling out other possible causes of memory problems, such as stress, depression, or medications, you can help yourself cope by incorporating these suggestions into your daily routine4:

  • Try relaxation training to help focus your attention.
  • Write in a journal or diary to see what influences your memory problems.
  • Set a routine or schedule that you follow consistently every day.
  • Ride it out—settle in for the day and watch television or funny movies.
  • Exercise; aerobic exercise helps your mood and increases alertness.
  • Alter your work environment or expectations: simplify.
  • Learn what your cognitive strengths are and capitalize on those. (What time of day is best for tackling tasks?)
  • Compensate for weaknesses by using external memory aids (daily planner, notes, maps, and reminder phone calls).
  • Discuss frustrations about slower moments with friends and family.

Regarding software products that are marketed as memory-building tools, Dr. Meyers says that repetitive mental exercises just don’t work. “You might get better at the specific game, but the skills don’t carry over to your life. For example, you might get better at Nintendo and still forget your friend’s name.”

Help from the Pharmacy

At this point no drugs have proved successful for combating the effects of brain tissue damage. A small study conducted by Sadhna Kohli, research assistant professor at University of Rochester, showed improvement in memory, concentration, and learning for people taking Provigil® (modafinil), a drug that stimulates the brain only as required and lasts about 12 hours. Unlike Ritalin® (methylphenidate), which some patients have tried, Provigil is nonaddictive.

It’s also important that doctors assess and treat possible contributing factors such as thyroid dysfunction, hormonal imbalance, or anemia. As researchers come to better understand the mechanisms of chemo brain, genetic factors may play a larger part in treatment plans.

Sharon has found help close to home. Her mother is also being treated for cancer. Staying active and having a sense of humor help, she says. “It’s really important to be around people who understand you’ve gone through treatment.”

Many Patients with “Chemo Brain” Recover within Five Years

A study of “chemo brain”—the foggy thinking and forgetfulness that patients may experience after chemotherapy—suggests that the condition improves substantially over time for a majority of patients. For some patients, however, symptoms may persist for more than five years after treatment. These findings were recently reported in the Journal of Clinical Oncology.

Chemo brain refers to changes in cognitive function, such as loss of memory and inability to think clearly or perform some daily functions. Researchers have not been able to pinpoint the cause of chemo brain, but current studies are evaluating brain structure and function in order to better understand the effects of chemotherapy on the brain.

To understand more about how chemo brain affects patients several years after treatment, researchers evaluated 92 patients at the Fred Hutchinson Cancer Research Center in Seattle. Patients had been treated for blood cancers with chemotherapy and bone marrow or stem cell transplants. The patients were matched with controls who had not undergone cancer treatment.

Standardized tests were used to assess cognitive function among all participants. The test measured cognitive functions including memory and motor skills. Findings were combined to create a Global Deficit Score (GDS), which summarized overall impairment. Results from patients were compared with results from controls.

  • During the five years following treatment, survivors were able to recover much of their cognitive function. Verbal recall (the ability to call up a known word—one that is on the “tip of the tongue”), however, was more difficult to recover than other functions.
  • Some functions, such as verbal fluency and executive function (including abilities such as planning and organizing) improved during the five years post-treatment, whereas motor skills did not improve during this time.
  • At five years after treatment, GDS indicated that 41.5% of survivors had deficits that were mild or greater compared with 19.7% of controls.

Though it appears that the cognitive impairment following chemotherapy known as chemo brain is largely temporary and likely to improve during the five years following treatment, difficulties persist for a significant number of survivors (more than 40%). An understanding of the risk factors and reasons for these lasting impairments is needed, as are improved methods to rehabilitate cognitive function.

Some Evidence of Mild “Chemo Brain” in Breast Cancer Survivors

Breast cancer patients treated with chemotherapy are at risk for mild cognitive deficits (sometimes referred to as chemo brain) after treatment, according to the results of a study published early online in the Journal of Clinical Oncology.

A large portion of breast cancer patients will ultimately receive adjuvant chemotherapy. Patients undergoing chemotherapy have long complained of a phenomenon referred to as “chemo brain”. Chemo brain refers to changes in cognitive function, such as loss of memory and inability to think clearly or perform some daily functions. Thus far, researchers have not been able to pinpoint the cause of chemo brain, but studies are ongoing to evaluate brain structure and function in order to better understand the effects of chemotherapy on the brain.

There is mixed evidence regarding the scope and duration of chemo brain. Many studies have not focused on the post-chemotherapy period and thus have produced little data regarding the long-term effects of chemotherapy on the brain.

Researchers from the Moffitt Cancer Center conducted a meta-analysis of 17 studies that included 807 patients previously treated with standard-dose chemotherapy for breast cancer. The goal was to evaluate cognitive functioning in breast cancer survivors more than six months after being treated with chemotherapy. The studies included neuropsychological tests categorized according to eight cognitive domains: attention, executive functioning, information processing, motor speed, verbal ability, verbal memory, visual memory, and visuospatial ability.

The results of the analysis indicated that patients treated with chemotherapy had mild impairments in verbal ability and visuospatial ability compared to non-cancer controls. Cognitive impairment varied across survivors; however, the researchers reported that age, education, time since treatment, and hormonal therapy did not seem to have an effect on the observed cognitive deficits.

The researchers concluded that, on average, cognitive deficits in breast cancer patients who were previously treated with chemotherapy are mild and are limited to verbal and visuospatial abilities. They suggest that this information can be used to educate patients regarding the long-term impact of chemotherapy so that patients can develop interventions and modifications to cope with cognitive effects. Breast cancer patients who experience cognitive deficits may need to visit a neuropsychologist for evaluation and coping strategies.

Chemo Brain Linked to Long-Term Changes in Brain.

Chemo brain appears to correlate with long-term changes in the brain’s white matter, according to the results of a study published in the Journal of Clinical Oncology.

Patients undergoing chemotherapy have long complained of a phenomenon referred to as “chemo brain”. Chemo brain refers to changes in cognitive function, such as loss of memory and inability to think clearly or perform some daily functions. Thus far, researchers have not been able to pinpoint the cause of chemo brain, but studies are ongoing to evaluate brain structure and function in order to better understand the effects of chemotherapy on the brain.

Researchers performed a controlled observational cohort study in order to evaluate cerebral white matter integrity before and after chemotherapy. The small study included 34 younger premenopausal women with early stage breast cancer who were exposed to chemotherapy, 16 patients who were not exposed to chemotherapy, and 19 age-matched healthy controls.

The women exposed to chemotherapy underwent cognitive testing and magnetic resonance diffusion tensor imaging (DTI) prior to beginning chemotherapy and again 3 to 4 months after treatment. The women in the other two groups underwent the same assessment at matched intervals.

Compared to both control groups, the women in the chemotherapy-treated group performed significantly worse on attention tests, psychomotor speed, and memory during the second round of assessment (3 to 4 months after chemotherapy). In addition, the chemotherapy group had significantly increased self-reported cognitive complaints. Furthermore, the DTI detected decreased white matter integrity in the brain areas involved with cognition in the women treated with chemotherapy—but no changes in the two control groups. The researchers speculated that there might be a causal relationship between chemotherapy exposure, cognitive complaints, neuropsychological test abnormalities, and white matter changes.

The researchers concluded that they found longitudinal changes in cognitive functioning and cerebral white matter integrity after chemotherapy—and an association between the two characteristics. This was a small study and research is ongoing to study chemo brain. This study adds to the mounting evidence that chemotherapy may have long-term neurological effects.

Older Chemotherapy Regimen for Breast Cancer Linked with Persistent “Chemo Brain”

Women who received CMF chemotherapy for breast cancer between 1976 and 1995 scored slightly lower than women with no history of cancer on tests of word learning, memory, and information processing. These results were published in the Journal of Clinical Oncology.

Studies of “chemo brain”—the foggy thinking and forgetfulness that patients may experience after chemotherapy—have suggested that the condition often improves with time. Some patients, however, may experience persistent problems.

CMF is a chemotherapy regimen that was once commonly used in the treatment of breast cancer. It involves a combination of cyclophosphamide, methotrexate, and 5-fluorouracil.

To explore long-term effects of CMF on cognitive function, researchers inEuropeconducted a study among 196 breast cancer survivors who had been treated with CMF between 1976 and 1995. The cognitive function of these women was compared with the cognitive function of more than 1,500 women who had never had cancer.

  • The cognitive test scores of the women who had been treated with CMF were slightly lower than the scores of the women who had never had cancer. Scores were lower in the areas of word learning, memory, and information processing speed.
  • The reduction in test scores among the CMF-treated women was comparable to roughly six years of age-related cognitive decline.

Although CMF is no longer commonly used in the treatment of breast cancer, there are many women currently alive who were treated with CMF in the past. For women who are experiencing subtle but persistent cognitive problems, coping strategies—such as developing systematic daily routines and preparing well for activities such as work or travel—may be helpful.

Some people appear to be more likely than others to experience long-term cognitive problems after chemotherapy, and researchers are looking into the reasons for this.

Knowledge is power. Are you facing a new diagnosis, recurrence, living with metastatic disease, or supporting a loved one through their cancer journey?

  • Get the facts about breast cancer here.
  • Join ongoing discussions with other individuals affected by breast cancer in the CancerConnect private online breast cancer community here.

Chemo Brain Linked to Long-Term Changes in Brain.

Chemo brain appears to correlate with long-term changes in the brain’s white matter, according to the results of a study published in the Journal of Clinical Oncology.

Patients undergoing chemotherapy have long complained of a phenomenon referred to as “chemo brain”. Chemo brain refers to changes in cognitive function, such as loss of memory and inability to think clearly or perform some daily functions. Thus far, researchers have not been able to pinpoint the cause of chemo brain, but studies are ongoing to evaluate brain structure and function in order to better understand the effects of chemotherapy on the brain.

Researchers performed a controlled observational cohort study in order to evaluate cerebral white matter integrity before and after chemotherapy. The small study included 34 younger premenopausal women with early stage breast cancer who were exposed to chemotherapy, 16 patients who were not exposed to chemotherapy, and 19 age-matched healthy controls.

The women exposed to chemotherapy underwent cognitive testing and magnetic resonance diffusion tensor imaging (DTI) prior to beginning chemotherapy and again 3 to 4 months after treatment. The women in the other two groups underwent the same assessment at matched intervals.

Compared to both control groups, the women in the chemotherapy-treated group performed significantly worse on attention tests, psychomotor speed, and memory during the second round of assessment (3 to 4 months after chemotherapy). In addition, the chemotherapy group had significantly increased self-reported cognitive complaints. Furthermore, the DTI detected decreased white matter integrity in the brain areas involved with cognition in the women treated with chemotherapy—but no changes in the two control groups. The researchers speculated that there might be a causal relationship between chemotherapy exposure, cognitive complaints, neuropsychological test abnormalities, and white matter changes.

The researchers concluded that they found longitudinal changes in cognitive functioning and cerebral white matter integrity after chemotherapy—and an association between the two characteristics. This was a small study and research is ongoing to study chemo brain. This study adds to the mounting evidence that chemotherapy may have long-term neurological effects.

References:

  1. Tannock IF, Ahles TA, Ganz PA, Van Dam FS. Cognitive impairment associated with chemotherapy for cancer: Report of a workshop. Journal of Clinical Oncology. 2004;22(11):2233-39.
  2. Chemo Brain. American Cancer Society Web site. Available at:. Accessed June 22, 2008.
  3. Abraham J, Haut MW, Moran MT, Filburn S, Lemiuex S, Kuwabara H. Adjuvant chemotherapy for breast cancer: Effects on cerebral white matter seen in diffusion tensor imaging. Clinical Breast Cancer. 2008;8(1):88-91.
  4. Chemobrain: When Cancer Treatment Disrupts Your Thinking and Memory. Mayo ClinicWeb site. Available at:.
  5. Syrjala KL, Artherholt SB, Kurland BF, et al. Prospective neurocognitive function over 5 years after allogeneic hematopoietic cell transplantation for cancer survivors compared with matched controls at 5 years. The Journal of Clinical Oncology [early online publication]. May 2, 2011.
  6. Jim HSL, Phillips KM, Chait S, et al. Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. Journal of Clinical Oncology. Published early online August 27, 2012. doi: 10.1200/JCO.2011.39.5640
  7. Deprez S, Amant F, Smeets A, et al: Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. Journal of Clinical Oncology. 2012; 30:274-281
  8. Koppelmans V, Breteler MMB, Boogerd W, Seynaeve C, Gundy C, Schagen SB. Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. Journal of Clinical Oncology. Early online publication February 27, 2012.

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