Chemo brain is a condition that many cancer patients deal with during and often after treatment. Not only can chemo treatments cause this condition, but also radiation, surgery, and immunotherapy. Being a cancer patient that has gone through 16 chemo treatments, 25 radiation treatments, and 5 surgeries, all within about 22 months, I can absolutely say that in my case, all of these factors combined took a toll on my physical and mental health as well as my memory and my ability to think clearly. My last surgery was one year ago, and I still have memory issues, but I have learned how to live with it by making a few changes in how I organize my life. This subject is something that I have been reluctant to write about, but now that my cancer has returned, I feel that it is time to post an entry about my experience so I will do that soon.
by Stephen Ornes
Many cancer patients have problems with memory or thinking that can linger for years after treatment. The cause is a mystery, but new tactics are helping many people cope with its effects.
BEFORE MEGAN-CLAIRE CHASE received her first round of chemotherapy in October 2015, her oncologist told her that side effects of cancer treatment could include some memory loss. “They said, ‘You might get a little forgetful. It will probably be minimal. Don’t freak out,’” she says. Chase, who was single, 39, and working in radio advertising in Atlanta, didn’t think much about it at the time. She was more concerned with treating the tumor and managing other unwelcome complications that cancer introduced to her life.
Chase had already seen her routines upended. A month earlier, she had discovered a large mass in her left breast and unusual bruises nearby. A diagnostic mammogram and biopsy led to a diagnosis of stage IIA invasive lobular breast carcinoma, which originates in the milk glands of the breast and invades nearby tissue before spreading to lymph nodes. Over the next few months, she would undergo 16 treatments with chemotherapy and 33 with radiation. During that time, she noticed a diminishing ability to think, reason and remember things.
She first noticed a problem with memory after her second round of chemo, when she was already feeling nauseated and losing her hair. She had gone to a store to pick up groceries. When she arrived home, she reached to take her purse from the car—only to find it wasn’t there. She stood, completely astonished, for a few seconds. Then she panicked and raced back to the store parking lot, where she found the purse untouched in the shopping cart.
“That was my first moment of dealing with chemo brain,” Chase says. She hadn’t simply forgotten the purse; this experience was something more than forgetting. “I literally had no memory of it. It’s not like I got stressed and forgot and remembered. It was just gone, like a void. It’s deeper than forgetting.” She suspects the only reason she realized the purse was gone was because she physically reached for it and had nothing to grab, not because she remembered leaving it behind.
The bedeviling, exasperating phenomenon that Chase describes goes by many names. Chemo brain. Brain fog. Mental fog. Chemo fog. Researchers who study it and doctors who see it in their patients call it cancer-related cognitive impairment, or CRCI. (Less often, it’s labeled cancer-related neurocognitive dysfunction, or CRND.)
Up to three-quarters of people treated for cancer experience cognitive problems that can be described as CRCI. Symptoms include forgetting words, names and dates. Some patients report being unable to follow conversations or control their emotions. Once-avid readers find themselves unable to maintain focus to the end of a chapter. “If they do get through it, it may be hard to remember what they just read,” says Natalie Kelly, a neuropsychologist at City of Hope Comprehensive Cancer Center in Duarte, California, who works with patients to identify problems with CRCI and map out coping strategies. Chase says that soon after her scare at the store, she became much less efficient at multitasking, which was a critical part of her job. She began to doubt herself.
For more than a third of people treated for cancer, CRCI symptoms persist for months or even years after treatment, in varying degrees of severity. In some cases, says Kelly, the cognitive troubles may subside, but stress can exacerbate symptoms. Serious symptoms are most often associated with chemotherapy, but chemo isn’t the only culprit. Patients who undergo radiation, surgery or immunotherapy have similarly reported cognitive difficulties.
CRCI poses a formidable puzzle. It has no formal diagnosis or treatments approved by the Food and Drug Administration (FDA). Researchers don’t yet know which patients are most vulnerable to CRCI, or why cancer treatment triggers CRCI at all. “It’s a complex problem,” says neuroscientist and cancer biologist James Bibb at the University of Alabama at Birmingham Heersink School of Medicine and O’Neal Comprehensive Cancer Center. “Every cancer is different, every patient is different, and every treatment is different.” Not surprisingly, every experience with CRCI is also different.
Yet there are recent signs of progress in understanding and treating the condition. “There’s a noticeable interest in what we can do to limit the neurological effects that some patients experience,” says Bibb. Researchers began to seriously study CRCI starting in the 1990s, says clinical neuropsychologist Nicolette Gabel at University of Michigan Health in Ann Arbor. The past two decades have brought increased attention to CRCI, not only among patients who share stories of lost keys and missing words, but also among clinicians and researchers looking for its biological causes and developing successful coping strategies.
“It’s not an uncommon problem,” Kelly says, adding that adopting lifestyle modifications—especially with the help of a trained cancer rehabilitation specialist—may compensate for the daunting mental challenges posed by CRCI.
Living Longer, Facing CRCI
Bibb says the increased attention on CRCI is a byproduct of significant progress in treating cancer and keeping people alive longer. The overall five-year survival rate for people diagnosed with cancer in 1980 was about 50%, according to data from the National Cancer Institute. By 2017, that overall rate had climbed to nearly 68%. Experts usually attribute the rise to early detection, improved treatment and smoking cessation. They also caution that the overall statistic smooths over important details. Survival rates are lower in Black populations and vary by cancer site. Dismal pancreatic cancer survival rates have barely budged in 50 years, while prostate cancer’s five-year survival rate is now close to 100%, for example.
What’s clear is that people are living longer with cancer. As a result, they are more likely to grapple with long-term effects of the disease and its treatment, including CRCI. “Cancer itself used to be the main issue, but now survivability and survivorship have become equally important,” says Bibb.
For Chase, the missing purse was the first of many instances she chalks up to CRCI. During chemotherapy and then radiation treatment, the problems snowballed. “I couldn’t remember how to do certain tasks at work that used to be second nature,” she says. “I had an inability to participate in conversations with people at work, and I wouldn’t remember full conversations with my mother. She would say, ‘You told me that 15 minutes ago.’” The mounting uncertainty led her to leave her job in radio advertising and find less stressful work.
Chase’s experiences also drove her to develop coping strategies, sometimes with the help of her therapist, who was an oncology social worker. “Any cancer patient needs a therapist,” she says. “Mine has the knowledge of what a cancer patient goes through and can provide guidance to help.” She also started writing a blog, called Life on the Cancer Train, to keep a record of her experiences and used social media to reach out to other people with CRCI to collect anecdotes for her writing. A common thread emerged among all the stories she heard: Everyone with CRCI suffered acutely from self-doubt, she says. How can a person trust their own mind when it keeps failing them?
Chase began to write down everything she needed to get done and set reminders on her phone. She also read long magazine articles out loud to herself. “It forced me to read words and concentrate,” she says. At first, she could only manage a few minutes of reading aloud, but over time her attention span grew. “It really helped strengthen my short-term memory.” Eventually, years after her treatment regimen had ended, she reached a point where she no longer had to write everything down. (“I still write down the super-important stuff.”)
Chase says she received little guidance from her health care providers about how to navigate the post-treatment fog. “It’s wonderful that they kept me alive,” she says. “But after, I felt like they just threw me out in the middle of the ocean with no life jacket.”
Gabel, at University of Michigan Health, says Chase’s experience is common. She recently led an analysis of existing studies and surveys focused on CRCI, and the group published its findings in Current Physical Medicine and Rehabilitation Reports in July 2021. The analysis revealed that many different symptoms that patients notice can be measured, and that these symptoms are often noticed as treatment progresses. The analysis also reported that patients can become distressed when they notice changes in the way they think, reason or behave.
“Educating patients about the risk for CRCI needs to be more of a strategic implementation at the beginning of cancer care,” says Kelly at City of Hope. “With more survivors, which is wonderful, there are more people living with the effects of treatment who want to understand how to live their best lives and move forward with their goals, even in the midst of experiencing cognitive issues.”
Many hospitals and cancer centers offer resources. These may include consultation with a trained neuropsychologist after treatment ends. The consultation usually begins with an evidence-based evaluation that can help guide the creation of an individualized treatment plan. The evaluation helps identify and measure the severity of cognitive impairment, including learning and memory tasks.
“We identify any factors that may contribute to CRCI,” says Gabel. “What makes it harder for patients? Insomnia, pain, other factors can get in the way.”
The resulting plan, based on evidence from existing studies, may include cognitive rehabilitation, in which patients work with trained therapists on interventions that can help create compensatory strategies to improve mental skills. (The same interventions are often used to help people with traumatic brain injury, stroke or other neurological impairments.) It may also include recommendations for lifestyle adjustments that could help reduce stress, which is known to trigger the effects of CRCI.
Exercise may help. Studies have shown that people with cancer who exercise regularly report less fatigue. More recent investigations suggest that exercise may help ease some CRCI symptoms, though more research is needed. Other studies have suggested improvements from cognitive behavioral therapy or from mindfulness-based activities. (See “Strategies to Manage Cognitive Impairment” below.)
Although no medications have been approved by the FDA to treat CRCI, recent studies have investigated whether psychostimulants (like methylphenidate) or anti-dementia drugs may offset the symptoms. These studies have reported promising results, but they are limited by small numbers of participants and inconsistent study parameters. They don’t reveal, for example, which patients are most likely to benefit from treatment. More evidence is needed before clinicians can recommend specific drug treatments, says Kelly.
Strategies to Manage Cognitive Impairment
Cancer-related cognitive impairment has no definitive diagnosis or treatments, but patients can use techniques to better cope with the condition.
According to the National Cancer Institute, nearly 17 million people in the United States are living with cancer or have been diagnosed in the past. Three-quarters of them—almost 12.8 million—likely experience problems with memory or thinking resulting from treatment. Sometimes the symptoms resolve, sometimes they persist, and sometimes they worsen in times of stress.
The condition, called cancer-related cognitive impairment (CRCI), has no definitive diagnosis and no treatments approved by the Food and Drug Administration, but there are strategies to better cope with its effects. These include:
Writing. Note everything to help remember important tasks.
Reading. One patient who received extensive chemotherapy and radiation regained a longer attention span by reading out loud.
Asking for help. Your oncologist at the hospital may refer you to a neuropsychologist, who can assess the severity of CRCI and recommend coping strategies.
Moving. Establish a regular regimen of physical activity.
Talking. A trained mental health provider such as a psycho-oncologist can help you process the emotional tumult brought on by CRCI.
Despite decades of studying CRCI, much work needs to be done, says Gabel. She and other researchers are now working to improve neurological assessments. “One of the difficulties has been to understand the correlation between what patients are noticing and what we are measuring,” she says. “Patients report much more severe symptoms than what we can capture on assessments.”
Then, there is the mystery of CRCI’s neurological origins. Although lab and animal studies suggest that chemotherapy alters cells in the brain and central nervous system, understanding of the exact biological process is incomplete, which makes it hard to treat.
There are some hints to what’s going on, though. Some researchers are looking for answers in the microbiome—the collection of bacteria, good and bad, found in the body. A January 2022 study in the European Journal of Cancer reported that treatment with probiotics prevented CRCI in patients with breast cancer.
Bibb says the development of CRCI likely spans many systems within the body, but his work focuses on the mechanistic effects in the brain and the possible influences of the immune system as well. “I think that we are altering brain function directly through potential neurotoxic effects of the drugs but also indirectly through the effects of chemotherapy on the immune system,” he says.
He points to a study on mice, published in January 2019 in Cell, in which researchers from Stanford University found that treatment with methotrexate, a chemotherapy used to treat many kinds of cancer, changed important immune cells in the brain called microglia, which in turn disrupted other processes in the brain. Microglia play a variety of roles, including breaking down dead or dying cells.
More recently, in August 2021, Bibb and his colleagues published a study in ACS Chemical Neuroscience that identified regions of the brain and biological processes that were disrupted when mice were treated with two common chemotherapies, cisplatin and gemcitabine. Those disruptions, Bibb says, correspond to changes in brain signaling and inflammation in the brain. He cautions that the study was done in mice, and findings in mice don’t always translate to benefits for people, but it does suggest a way forward in understanding the consequences of chemotherapy for the brain.
Bibb believes that research will lead to a treatment for CRCI. “I absolutely see it as targetable,” he says. “We may be able to provide drugs that can prevent those effects or add a therapy that compensates for the indirect causes.”
Chase says that in the six years since she ended chemotherapy, her symptoms have partially subsided, though “I’ll never be at 100%.” One thing she learned, however, was the value of identifying her passions and interests, and finding ways to cultivate them. For her, that meant trying to get back on the stage. “My love of theater has always been there.”
In 2021, she enrolled in a six-week class at Alliance Theater in Atlanta. The class culminated in a performance of a two-person scene before an audience. To her surprise, she found that she could remember previous experiences in dramatic performances—where to move during a scene and how to memorize lines, for example. The night went off without a hitch. (Well, almost: At the last minute, Chase had to change roles, but the audience was none the wiser.)
“It was such a personal victory,” she says. “I didn’t know how much time and therapy and confidence it would take to believe in myself again. At the end of the day, all of those side effects, and cancer, can’t take away the essence of you.”
Stephen Ornes, a contributing writer to Cancer Today, lives in Nashville, Tennessee.