'Chemo Brain': MRI Shows Brain Changes After Chemotherapy

Fran Lowry

November 16, 2011

November 16, 2011 — Breast cancer survivors who have been treated with chemotherapy show significant changes in brain activity, measured by functional magnetic resonance imaging (fMRI), according to a study published in the November issue of the Archives of Neurology.

The finding validates patients' claims of reduced cognitive function after receiving chemotherapy, a phenomenon referred to as "chemo brain," said lead author Shelli R. Kesler, PhD, from Stanford University School of Medicine in California.

Dr. Shelli Kesler

"Emerging research shows that there is a biological correlate of these cognitive problems that these patients are reporting," Dr. Kesler told Medscape Medical News. "Historically, there has been some controversy as to whether these problems really exist, so looking at the brain and seeing that there are brain changes validates patients' experiences."

She added that she hopes these findings will be helpful for breast cancer survivors who are experiencing such problems, "so that they are less likely to be turned away for things like disability benefits or even to be ignored by their physicians, who sometimes tell them that they're just imagining the problem. Our study shows that there really is a problem. It's not just stress. It's not their imagination. It's a real brain change."

Performing Card-Sorting Task

In this observational study, Dr. Kesler and her team sought to ascertain differences in prefrontal executive function between 25 breast cancer survivors who underwent chemotherapy, 19 women who did not, and 18 healthy women with no history of breast cancer. All subjects were matched for age and other demographic variables.

All women underwent fMRI while performing a card-sorting task that was designed to measure prefrontal brain activation associated with executive function and while performing a control task in which they were asked to judge whether a single card was red.

All 3 groups showed a similar profile of brain activation during the fMRI tasks, including bilateral cerebellum, basal ganglia, and parietal and dorsolateral prefrontal regions.

However, the results showed that the women with breast cancer demonstrated significantly reduced activation of the left middle dorsolateral prefrontal cortex and premotor cortex, compared with the healthy women.

In addition, breast cancer survivors who received chemotherapy showed significantly reduced left caudal lateral prefrontal cortex activation, increased perseverative errors, and reduced processing speed, compared with the other 2 groups.

The researchers also found that this reduced activation in the left caudal lateral prefrontal cortex was significantly correlated with higher disease severity and self-reported executive dysfunction in the chemotherapy group.

Groundbreaking Study

Dr. Michelle Janelsins

Michelle C. Janelsins, PhD, from the James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, in New York, told Medscape Medical News that she thinks this study is "groundbreaking, excellent, and extremely interesting."

"What is most interesting about this study is that Dr. Kesler and colleagues were looking at specific areas of the brain and trying to associate these areas with specific types of processes, such as problem solving, decision making, and planning," Dr. Janelsins said.

"We are always looking for indicators of subclinical problems that might predict longer-term impairment so that we can manage them if it looks as if the person is developing cognitive deficits," she said. "Not every single individual develops cognitive deficits; brain imaging may be a way to allow us to determine who is most at risk and who is most affected by chemotherapy for breast cancer."

"Chemo Brain" Not All in the Mind

Dr. Kesler said that older women and those who were less physically and mentally active were more likely to be cognitively affected by chemotherapy.

"Two of the things we found that predicted more cognitive dysfunction were age and cognitive reserve, so the older you are, the more vulnerable, which is not surprising since you are more vulnerable to a lot of things," she said.

"When you have been more mentally and physically active, [cognitive reserve] tends to give you more brain capacity, so when something like breast cancer and chemotherapy happens to you, you have more capacity to overcome that," she said.

Dr. Kesler hopes this research will lay the foundation for future longitudinal studies that will evaluate patients before and after chemotherapy. "These are going to be critical for figuring out this problem. It's hard to get funding to do those studies unless you have evidence such as that from our study, showing that cognitive dysfunction is a real problem."

This study was supported by the National Institutes of Health. Dr. Kesler and Dr. Janelsins have disclosed no relevant financial relationships.

Arch Neurol. 2011;68:1447-1453. Abstract

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