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Making Sense of Chemo Brain


Cancer-related cognitive dysfunction affects many survivors. But the right strategies can optimize thinking and memory — and help lift that fog.

In August 2019, Andy Nelli, 68, went to Cedars-Sinai Medical Center in Los Angeles for an infu- sion of Rituxan (rituximab), Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), Oncovin (vincristine) and prednisone — known as R-CHOP chemotherapy — followed by a dose of metho- trexate delivered through a spinal tap to treat her non-Hodgkin lymphoma. Later, she woke from a nap to find two business cards on the table by her bed.

A friend who works at the hospital had mentioned that two oncology social workers would be stopping by to see her. “I called my friend and said, ‘I must have been sleeping when they stopped by,’” Nelli says. “‘No,’ my friend said, ‘You were awake, and they said they had the best conversation with you.’”

That was the moment Nelli knew something changed.

“I had zero recollection of the conversation,” she says. “When they came back the next day, it wasn’t, ‘Oh, I remember you.’ I had no idea who they were.”

Today, chemotherapy is behind her. But “chemo brain” — also known as cancer-related cognitive impairment or cancer-related cognitive dysfunction — isn’t, Nelli says.

“Even this morning, I wanted to wear comfy shoes for a walk, so I cleaned my cute white shoes with the thick soles,” she says. “Then I put them down, got dressed in black pants and thought, ‘OK, I’m wearing black. Let me get out my black shoes to wear.’ I forgot I had just cleaned the white shoes to wear until I saw them on the floor.”

Nelli isn’t alone. Between 17% and 75% of survivors treated with chemotherapy, hormone therapy or radiation therapy experience cancer-related cognitive dysfunction.

Many patients experience some cognitive problems while they’re being treated with chemotherapy, and about a third of survivors experience cognitive issues after treatment has ended, according to Todd Horowitz, PhD, program director at the behavioral research program’s biobehavioral and psychological sciences branch in the Division of Cancer Control and Population Sciences at the National Cancer Institute in Bethesda, Maryland.

The data on cancer-related cognitive impairment are complicated, due somewhat to a lack of long-term information about survivors and how their cognition changes over time. But as the number of survivors increases, so do the opportunities to study the issue, says Cara Pendergrass, PhD, assistant professor in the clinical psychology department at William James College in Newton, Massachusetts, who studies cognitive impairment associated with cancer. She stresses that when it comes to cancer-related cognitive dysfunction, there are no absolutes.

“There’s a lot of individual variability in those who are experiencing cognitive changes after cancer treatment,” she says. “What we see is that this can continue for several months or for several years in some cases.”


What exactly causes cancer-related cognitive impairment? Is it the cancer itself? Is it the treatment? Or both? The answers are not clear.

“Brain cancers are in a whole different category, and if you have a central nervous system tumor, that’s going to have a cognitive effect,” Horowitz says. “The treatments for these cancers may involve (exposing the brain to radiation), which is not good for cognition. But outside of the central nervous system, for cancers like breast cancer or colorectal cancer, we don’t see data indicating ... big differences by cancer site.”

Identifying the cause of cognitive impairment is tricky because there are so many factors, according to Pendergrass. “We know it’s related to the size, location, momentum and malignancy element of the cancer,” she says.

“We know that how treatments impact cells and cell functioning can lead to changes in cognitive function, but we also know those factors may interact if an individual has a preexisting condition like diabetes or high blood pressure. (Also having an impact are such things) as how long an individual has undergone treatment and if chemotherapy was combined with adjunctive treatment like radiation or hormone therapy.”

Arash Asher, M.D., director of Cancer Survivorship and Rehabilitation at Cedars-Sinai Medical Center, says cognitive impairment may be linked to an immune system response. “Anyone who’s had the flu knows you feel tired and can’t concentrate,” he says. “That’s your immune system’s response. We know the body produces cytokines in response to the flu to make you feel tired and foggy. It’s nature’s way of making sure you stay home resting. What we’re learning is that when you have a cancer or chemotherapy, your body responds with a similar mechanism. Many people believe it’s these cytokines crossing the blood-brain barrier and contributing to these cognitive symptoms.”

Given the links between chemo- therapy treatment and cognitive impairment, are certain chemo- therapy drugs more likely to cause these symptoms? Not really, says Asher. “The science is by no means clear enough to say that chemo drug A is more likely to cause these problems than chemo drug B,” he says. “Given that it’s not clear, we shouldn’t deny someone the drug that may be best for their cancer type.”

In a recent article published in Innovations in Clinical Neuroscience, Pendergrass and her co-authors noted that elevated levels of cytokines might contribute to cognitive deficits — as might DNA damage from cancer itself or chemotherapy. Additionally, expecting that you’ll experience cognitive changes can be a contributing factor for some people. In one study, people treated with chemotherapy who were told they might have cognitive side effects were more likely to report problems than people with comparable treatment who had not

been told they might have cognitive side effects. Still, there are positive outcomes from having conversations about treatment side effects, and it’s important to talk with your doctor about any side effects that may or may not occur.


Laura Schneider, 64, who lived in Basking Ridge, New Jersey, when she was diagnosed in 2006 with late-stage ovarian cancer, was treated with four rounds of cisplatin and Taxol (paclitaxel) after partial debulking surgery. After a second surgery, which included a hysterectomy, she received four additional rounds of cisplatin and intraperitoneal Taxol.

She was diagnosed with triple- negative breast cancer in January 2019, underwent a double mastectomy and reconstruction in April 2019 and completed four rounds of chemotherapy in July 2019.

“Chemo fatigue is the gift that keeps on giving,” she says. “Word retrieval became pretty much impossible. I’d be at dinner and say, ‘Would you please pass the’ — then couldn’t remember the word,” she says. Schneider, who works as a patient advocate and is a support volunteer with the Cancer Hope Network, a New Jersey-based nonprofit organization that offers support for people with cancer, encourages survivors to speak with their doctor about cognitive symptoms.

“You’re not crazy,” she says. “Chemo brain is very real, and it affects people differently.”

Just how differently is one of the challenges for researchers and doctors. Horowitz says that whether a person notices signs of cognitive impairment may depend on how much “heavy mental lifting” they’re expected to do. Those who are no longer working at jobs that require significant focus or concentration might not notice a degradation of their mental faculties.

“Also, being able to notice and measure your own level of cognition is itself a cognitive function,” he says. “Unless it’s called to your attention, you might not notice you’re forgetting things.”

Generally, cognitive function is evaluated in two ways: objective testing and subjective evaluation. Perceived cognitive change, or how a person thinks they’re doing with cognitive tasks, is a subjective measure, Pendergrass says. Objective evaluation includes standardized tests that evaluate measures such as attention and short-term memory.

One example of an objective evaluation of verbal learning and memory is reading a list of 12 to 16 words aloud to a survivor, who then immediately repeats as many words as they can remember. “Then we wait about 20 minutes and ask the person to repeat as many of the words as they can again,” Pendergrass says.

Subjective evaluations include questionnaires with statements like, “I feel my thinking is slower” and “I think I have trouble concentrating.” Subjective tests might also include questions about whether a partner or friend has noticed things you might not notice, says Horowitz.

Asher says subjective assessments weigh heavily in his evaluation of cognitive impairment in cancer survivors. “I prefer the subjectivity because it tells me what the person is feeling and experiencing,” he says. “Whatever the cause may be, you can’t deny someone’s experience.”

The challenge of evaluating cognitive impairment, however, lies in the “murkiness,” notes Asher.

“Often, there’s little correlation between objective findings and what the patient says they’re experiencing,” he says. “One explanation may be that tests don’t replicate the real world. In testing, you’re sitting in a quiet exam room with no distraction and a psychologist guiding you to answer questions. That may not replicate all the multitasking that goes on in the real world. Another is that there may be other factors in the survivor’s experience, like anxiety or depression, that testing may not be able to depict.”


Asher runs a six-week program at Cedars-Sinai called, “Emerging from the Haze.” “It’s 12 hours of content on how people with cancer-related cognitive impairment can optimize their lifestyle and develop compensatory strategies,” he says. The program focuses on the science behind getting good sleep, exercise and nutrition; managing stress and moods; and managing symptoms of depression. “Even though it’s not the same, there’s a lot of overlap between symptoms of depression and symptoms of cognitive dysfunction, especially subjectively,” he says.

Nelli says the program gave her tools to manage her cognitive symptoms, and, just as important, a community that made her feel like she wasn’t alone. “This was a real opportunity for me to swap stories,” she says. “And that helped me realize this wasn’t just happening to me.”

Among the strategies she uses, especially when completing multistep tasks, is calling out each step as she does it. “If I’m making something with a lot of ingredients, I’ll say out loud, ‘I’m getting the butter’ and ‘I’m getting the bell peppers.’ It helps,” she says.

Nelli, who works as an interior designer in the hospitality field, also relies on bullet points to help her organize and manage

her work tasks. “Every day, I write the date and bullet point all the things I have to do,” she says. “Then I write down what I’ve done that day and where I left off, so I’m able to read back.”

Schneider says she’s become a big list- maker. “Even my lists have lists,” she says. “I (also) started documenting conversations. It’s a strategy I used while teaching and documented conversations with parents.

I have a journal filled with conversations to help me remember what I have discussed.” Both Nelli and Schneider say technology is a big help.

Nelli reads back through texts and emails for a historical conversational record, and Schneider sets alarms on her phone to help her remember what she needs to do at certain times.

“The fact that I have these alarms and they go off periodically is sometimes embarrassing,” she says. “More often, it’s just annoying.”

Pendergrass recommends survivors avoid multitasking if they find it difficult. Focusing on one task, such as paying bills, in a place without distractions can help, she says. Also helpful is talking to your primary care doctor about what you’re experiencing. “If possible, explain how the cognitive change is affecting your functioning specifically,” Pendergrass advises.

Focusing on good health basics — such as getting regular moderate aerobic exercise, eating nutritious foods and getting enough sleep — is important, Asher says, as is strengthening social ties. “Loneliness is highly correlated with cognitive symptoms in our study,” he says, adding that his recent study of “Emerging from the Haze” participants found that loneliness lessened — and cognitive symptoms improved — when “you’re sitting with a group of people who are walking through what you’re walking through.”

Asher also tells survivors to focus on what they can control. “We can’t change what we had to go through or the chemotherapy we had,” he says. “But there are a lot of things we can take advantage of to optimize cognitive health.”

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