Unraveling the Mysteries of Chemo-Brain

photo of Jamie Meyers, Ph.D., RN, AOCNS

WHEN CAROLYN HANSON STARTED CHEMOTHERAPY for ovarian cancer in 2016, she noticed that she was having to concentrate harder to read. She suspected her mental fuzziness was caused by the sleep deprivation and anesthesia from the surgeries she’d undergone to begin her treatment, compounded by a gastrointestinal bug. But her difficulties with thinking and remembering persisted for months after the chemotherapy ended. A bass guitarist in a rock band, Hanson even began having trouble with her music.

“I had forgotten all my bass lines,” she said. “Every last one. I had to relearn them all.”

Hanson is not alone. Nearly three-quarters of cancer patients experience a kind of mental fog that accompanies treatment, especially chemotherapy, and can last for months after treatment ends. This condition has been dubbed chemo-brain. A talented multi-tasker suddenly might find herself unable to keep track of her schedule or remember her home address. Trouble retrieving the right word is a classic complaint.

“It was particularly galling if it happened when I was in a meeting at work,” Hanson said.

A decade ago, health care providers typically did not talk to cancer patients about cognitive changes. Instead, patients were left doubting themselves while coping with symptoms that affect their quality of life and sometimes even their employment. When Hanson, who works as an IT project manager, landed back on the job market at the same time she was struggling mentally, she prepared for interviews if she were cramming for an exam, for skills for which she had certifications.

“I was really frightened that I was going to freeze during the interview,” she remembered.

Today, thanks to the work of people like Jamie Myers, Ph.D., RN, AOCNS®, research assistant professor at the University of Kansas School of Nursing, chemo-brain is now understood as an authentic condition.

Myers had spent 20 years as an oncology nurse administering chemotherapy but was unaware of the mental haze patients can experience. After she returned to the KU School of Nursing to pursue her doctorate, she listened to a panel discussion that included a breast cancer patient who had worked as an intensive-care nurse. The patient had not returned to the ICU after treatment because she didn’t feel equal to the job’s mental challenges.

“She actually had to change jobs,” Myers said. “That’s when a light bulb went off for me. I knew that addressing this problem was where I wanted to focus my research.”

Myers could find very little written that offered even a cursory description of chemo-brain, let alone any protocol for advising patients about it. So that’s where she started. In 2012, she published a study describing the cognitive impairment of many breast cancer patients and the mechanisms they used to cope, including simple strategies such as writing things down and doing more exercise. That study helped provide a framework for understanding these mental changes and developing educational tools for patients. Today, far more cancer patients are warned about cognitive difficulties, including trouble with language, concentrating and remembering.

Cathy Glennon RN, MHS, OCN, NE-BC, director of patient and community education at The University of Kansas Cancer Center, says when cancer patients talk to her about their new mental struggles, the first, and maybe most important, thing she does is validate their experience.

“I say it’s a legitimate concern and that it’s good they brought it to my attention, and then I give them some ways to deal with it: for example, keeping a detailed planner so they don’t miss appointments and using a pill box for medications,” said Glennon.

Elizabeth Muenks, Ph.D., a psychologist with the onco-psychology program at the KU Cancer Center, has a handout she gives to cancer patients that includes a list of simple strategies to can help reduce the impact that cognitive difficulties can have on everyday life.

“Patients can be very frustrated, so I do a lot of validating and explaining that these symptoms are real and can get in the way. I share ideas on how to cope by writing things down and coming up with a reminder system,” Muenks said. “I also encourage them to talk to their family and friends about it so they can be supportive.”

LOOKING AT CHEMO-BRAIN BIOLOGY

No medications are currently approved to treat chemo-brain nor has one cause been identified, although several possible contributors have: neurotoxicity from treatment; stress; genetics; and chemotherapy-induced menopause for female patients.

Myers is also focusing on how genetics and body mass index may be a factor in chemo-brain. Extra weight causes inflammation, which causes the body to produce more cytokines, which are proteins that regulate the immune system. Cytokines impair learning and memory in animals, suggesting they could contribute to the mental decline of cancer patients. Myers’ preliminary analyses of saliva samples from breast cancer patients indicate that some people may have a genetic variant that could provide some protection from cognitive decline.

Myers believes the role exercise plays in decreasing reports of chemo-brain could be her most significant finding so far. In a study she and her colleagues published in 2015, they found that excess weight (higher BMI) was associated with decreased reports of cognitive function in breast cancer patients. However, exercise frequency was associated with better cognitive function –even for patients who had a high BMI.

“Exercise reduces inflammation, increases blood flow to the brain and also helps to mitigate cancer-related fatigue, helping to improve cognitive function,” she explained.

DEVELOPING AN ASSESSMENT TOOL

Chemo-brain affects patients with many types of cancer, but Myers has focused mostly on breast cancer patients, a well-organized group that has been outspoken about cognitive issues.

“My ultimate goal is to be able to prevent chemo-brain or correct it as soon as it begins,” Myers said.

But first, there needs to be a way to measure the condition. One reason that cognitive issues weren’t recognized for so long is that cancer patients compensate for them by trying harder. For example, Carolyn Hansen said that just as she worked to regain physical fitness after chemotherapy, she also worked on brain fitness ‒ writing and doing logic and jigsaw puzzles. But there is no measure for the extra effort that patients like Hanson make.

Myers and Hannes Devos, Ph.D., assistant professor in the KU Department of Physical Therapy and Rehabilitation Science, want to change that. They recently published the results of a Frontiers pilot grant study that used eye-tracking software to measure the cognitive effort of breast cancer patients doing neurocognitive tasks. The more effort it takes, the more the pupils dilate. They compared 23 women with breast cancer who had undergone chemotherapy with 23 women who had not had breast cancer. The software measured how much the women’s pupils dilated during mental tasks, such as memorizing a sequence of numbers and letters.

They found what they’d anticipated: the women with breast cancer did about as well on the cognitive tasks as the cancer-free women, but their pupillary response showed that it took more effort, suggesting that women undergoing cancer treatment are compensating for a cognitive decline.

Myers and Devos are now conducting a sub-study that uses the eye-tracking software to measure the cognitive effort that women undergoing treatment expend while driving. This spring, 40 of the original participants performed a cognitive task while “driving” one of the medical center’s new portable driving simulators. Developed by Abiodun Akinwuntan, Ph.D., MPH, MBA, dean of the KU School of Health Professions, the simulators feature a scaled-down car cockpit and computer screens simulating road conditions. The driving simulation also enables Myers and Devos to increase the cognitive load with concurrent cognitive tests and to add two cognitive measurements for visual spatial ability and response times.

“Ultimately, we want to use this eye-tracking technology to evaluate interventions for chemo-brain,” said Myers. “A bigger dream is that it could be used to assess people going through cancer therapy, instead of assessing them with something more complex and expensive such as an MRI.”

Myers and Devos are also planning a study that uses the eye-tracking software on women who have just been diagnosed as a baseline assessment and then measure the cognitive change after treatment. They could then compare their results with results from functional MRIs. If the results are comparable, the eye-tracking software could provide a relatively inexpensive and less burdensome way to evaluate chemo-brain.

PUSHING SCIENTIFIC AND GEOGRAPHIC BOUNDARIES

Last year, Myers attended the annual Oncology Nursing Society Congress, where she met a nurse scientist from Hiroshima University interested in investigating speed feedback therapy, which combines aerobic exercise with mental stimulation. The subject rides a portable cycle connected to an iPad loaded with cognitive games. Some studies have shown that this kind of therapy improves cognitive function in elderly people with mild cognitive impairment, and one preliminary study has been conducted in survivors of breast and prostate cancer with positive results. Myers is working to set up a collaboration between KU, Hiroshima University, Indiana University and Centura Health in Colorado to test the efficacy of this intervention for cancer patients. If all goes as planned, this international study will begin in 2019.

Meanwhile at home, she’s collaborating with Sally Maliski, Ph.D., RN, FAAN, dean of the KU School of Nursing, who is conducting a prostate cancer study on men receiving androgen-deprivation therapy. That therapy suppresses testosterone, which can also impair cognitive function. When Myers learned about Maliski’s study, they quickly decided to seek funding to add a cognitive component. Maliski’s KU Cancer Center pilot award made the addition of prospective cognitive testing a reality for this study population.

When they began enrolling patients to the sub-study this year, it marked Myers’ first research on chemo-brain that is not related to breast cancer.

“The NCI is encouraging research that is inclusive of other types of cancer because chemo-brain is not isolated to breast cancer,” said Myers. “We would love to expand our work even further to other tumor types.”