Presented by: Shelli Kesler, PhD
Assistant Professor, Psychiatry and Behavioral Sciences
April 18, 2012
Memory and attention problems seem to be a common complaint among cancer survivors. Many people refer to these cognitive changes as “chemo brain,” but the cause and extent of these issues is not always a direct correlation to cancer therapy. Studies show that between 20 to 75 percent of cancer patients report problems with memory, attention, and thinking.
Shelli Kesler, PhD, an assistant professor of psychiatry and behavioral sciences and director of the Neuropsychology and Neuroimaging Laboratory at Stanford, described the research taking place to understand cognitive changes in cancer patients at a lecture sponsored by the Stanford Supportive Care program.
There are several components to cognition that can be affected by cancer therapy. The most common aspect is executive function, which includes the mental skills that help you adjust to the environment and organize goal-oriented behavior, such as problem solving, multitasking, planning, making adjustments, and controlling behavior. Effects to attention include forgetfulness, distraction, inconsistency, and lack of follow-through. Memory changes include forgetfulness, word loss, difficulty learning new things, and losing track. In all these types of cognition, processing speed can slow down, leading to inefficient thinking.
“Executive function, for example, is the best predictor of how well a patient with breast cancer can follow medication and treatment regimens,” said Dr. Kesler. “Keeping track of meds is a big strain on executive function, so these patients may have trouble complying with treatment.”
Though her work focuses on breast cancer survivors, she said that research findings may be applicable to other types of cancer as well. The challenge is that many factors may be involved in brain changes after cancer, ranging from chemotherapy to inflammation, genetics, hormones, and the tumor itself.
The body’s blood-brain barrier naturally protects the brain from most chemicals. Some chemotherapies like methotrexate and 5-FU can cross the barrier and impact neural stem cells; others, like doxorubicin and paclitaxel do not cross the barrier but seem to affect neural stem cells all the same—perhaps because minute amounts still get in the brain, she said. “A small amount may be all it takes,” she said, since these drugs are so toxic to neural stem cells.
Inflammatory molecules known as cytokines can also cross the blood-brain barrier and cause local inflammation and neurotoxic damage. Another cause in women may be estrogen deficiency, since the hormone is vital for brain function and can regulate inflammatory response. Other factors may include physical and mental activity, age, and genetic variations that might predispose a person to vulnerabilities.
Imaging the Brain
Dr. Kesler is using magnetic resonance imaging (MRI) to look at the structure, function, and connectivity of the brain and to track its changes over time. MRI uses magnets and radio waves to create detailed images of the brain, which can be consolidated to show accurate three-dimensional volumes and areas of activity.
In one study, she divided women into two groups: breast cancer survivors who had undergone chemotherapy and women without cancer. On average, treatment ended five years before the study. After comparing the groups in tests designed to assess learning and remembering words, she found that breast cancer survivors had lower activation in the prefrontal cortex when learning and overactivity throughout the brain when trying to remember. “They performed the same as controls on the tests in terms of accuracy, but they were slower and had to work harder,” she said.
In a follow-up study, the researchers found that breast cancer patients, regardless of whether or not they had chemotherapy, showed lower prefrontal activation. But the women who had had chemo had poorer performance, and rated themselves as having significant executive function problems. The study received a lot of media attention, she said, because it validated the patient experience of “chemo brain,” which historically has been dismissed or ignored for many patients.
Follow-up research focused on the hippocampus, a structure in the brain vital for learning and memory. Because it is a continuous source for neural stem cells, it may be particularly vulnerable to chemotherapy and inflammation. Dr. Kesler’s study showed breast cancer survivors had a lower volume in the hippocampus and scored lower on memory tests compared to healthy women.
“There are physiological changes taking place in the brain (after cancer treatment). Brain networks are less organized, and the frontal lobe and temporal regions are less integrated into the network. These are areas that affect executive function and memory,” said Dr. Kesler. “Our studies show a pattern of brain injury after breast cancer and chemotherapy. It validates the phenomenon of the cognitive effects of treatment.”
Other research has shown that women experience cognitive decline long after the chemotherapy is over. One study showed that 73 percent of breast cancer patients showed immediate decline after chemo but stabilized after one year. Of that group, 71 percent showed continued decline and 29 percent showed new difficulties after one year even though they had had no problems at the beginning.
Dr. Kesler is preparing a new study to understand why some women recover and some don’t, and who is at most risk for developing cognitive effects.
Assessment and Treatment
“The brain is the most complex system that we know of and involves a great deal of individual variation. This makes it incredibly difficult to diagnose and treat cognitive problems,” said Dr. Kesler.
Though there is no one standard test for assessing chemo brain, a neuropsychological evaluation can help profile personal strengths and weaknesses. An evaluation involves gathering background, tests, a report, and treatment plan focused on the patient’s concerns and goals.
Treatment can range from different types of medication to cognitive rehabilitation, which focuses on practical therapies to develop new skills and strategies as well as stress management. The technique involves a lot of home practice and technology like smart phones but is not widely available and patients must be referred by a physician or care provider.
Dr. Kesler said that it is also important to deal with the stress, anxiety, and depression related to cancer therapy, as well as fatigue, since these conditions can also affect cognitive function.
“You can improve cognitive function by enriching your environment with mental stimulation,” she said. “The brain is like a muscle and needs exercise.”
She recommended physical activity and mental challenges to stimulate the brain, such as puzzles, active journaling, novels, and specially designed online games.
About the Speaker:
Shelli Kesler, PhD, is an assistant professor of psychiatry and behavioral science and director of the Neuropsychology and Neuroimaging Lab at Stanford. She is a member of the Stanford Cancer Institute and the Bio-X Program. Her work focuses on understanding and treating cognition deficits associated with medical problems, particularly cancer. Dr. Kesler attended Brigham Young University, where she received her PhD in clinical neuropsychology. She did her residency at Adolescent Residential Treatment and Evaluation Center in Utah and her internship at the University of Utah Medical Center.
About the Series:
The Ernest Rosenbaum Cancer Survivorship Lecture Series is named after the noted oncologist who established the cancer supportive program at Stanford and the comprehensive cancer care program at UCSF’s Mount Zion Hospital. He wrote more than 25 books on cancer, most of them on living through treatments and life after cancer. The series is sponsored by the Stanford Supportive Care Program.
For More Information
About Dr. Kesler
Stanford Neuropsychology and Neuroimaging Lab
Stanford Behavior Medicine Clinic
Department of Psychiatry
Stanford Cancer Center
Sources for brain exercises