When Joyce Miner went through cancer treatment eight years ago, she expected to lose her hair. She didn’t expect to lose her mental edge. The hair has long since grown back and her acute lymphocytic leukemia is a closed chapter. But since her chemotherapy and stem cell transplant, her once rock-solid memory frequently falters. She can’t multitask, she depends on written lists to navigate her days and the grocery store, and she struggles to find the right words.
Mild cognitive impairment following cancer treatment is one of the most common symptoms reported by cancer survivors. This troubling deterioration in cognitive function is commonly called “chemobrain” or “chemofog,” though the names are somewhat misleading since chemotherapy may not be its sole cause.
The condition encompasses a range of problems much like those linked to aging. Patients cannot remember where they put their keys or recall lists of things they had planned to accomplish. Some say they are easily distracted or lose the ability to calculate in their heads. Survivors report diminished quality of life and daily functioning, and the impairment comes at economic, emotional and interpersonal costs.
But a growing body of research on chemobrain in the last decade has better defined the condition, and studies are beginning to lift the fog and reduce some quality-of-life impacts that can accompany the condition.
“My biggest loss is my memory,” Miner said. “I stumble on words and names. I know I know them, but I can’t summon them. It’s very unnerving because I’ve always had such a good memory.”
A Seattle-area real estate agent with her husband, Rick, for 15 years before her diagnosis, Miner now works fewer hours as a concession to her brain changes. She still shows homes to prospective buyers and handles basic paperwork, but leaves the rest to her spouse. “I can’t negotiate contracts anymore,” she said. “I just get lost. I’m conscious that I don’t sound like I know what I’m talking about.”
Frequent falls four years ago led Miner to a neurologist who confirmed her fears that her brain was impacted by her cancer treatment. “He said, chemobrain is not a myth. It’s a reality. I can see it in your brain scan.’ He described my brain as a big oak tree whose top leaves had been blown away—it’s like the ends of my brain burned off.”
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A tip-of-the-tongue frustration
The prevalence of chemobrain is hard to pin down, with estimates of cancer patients affected ranging from about 14 percent to as high as 85 percent. While researchers agree that its occurrence is much more dependent on the type of treatment than on the specific type of cancer, little is known about who is most likely to suffer a long-term deficit or how to guard against it.
Dr. Karen Syrjala
“It’s frustrating not to know who’s at risk, and we don’t have a strategy for prevention at this point,” said Dr. Karen Syrjala. As co-director of the Hutchinson Center’s Survivorship Program and director of the Biobehavioral Sciences group, Syrjala and her colleagues are leading cutting-edge research on the long-term outcomes of chemobrain.
“But if you’ve had high-dose chemotherapy, we know that you’re highly likely to have deficits across the board. We can see changes when we do imaging of the brain. Treatment hits people hard.
“In our research, the most common problem we hear is difficulty finding words or names—the tip-of-the-tongue experiences. You see a good friend in the grocery store and you know their name as well as you know your own but your brain can’t seem to pull the right strings to retrieve the name,” she said.
People also frequently report short-term memory issues and difficulties with fine-motor and hand-eye coordination.While most people recover, the process may be slower than they wish. There may be some areas that don’t recover 100 percent, but research shows that the majority of survivors function well in the world. About 30 percent of patients have long-term cognitive effects.
Because of the widely divergent patient experiences, studying the cognitive consequences of cancer treatment has been problematic. In some cases, those complications have led to a disconnect between patient experiences and attention to the issue.
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Not a phantom fog
“I think it’s probably true that there’s still a fair amount of skepticism amongst people about how real of a phenomenon this is,” said Dr. Timothy Ahles in the Journal of the National Cancer Institute. A frequent collaborator with Syrjala, Ahles is a cognitive psychologist at Memorial Sloan-Kettering
Cancer Center in New York. “Even though patients have been talking about this for years, really since the 1970s, it’s only in the last 10 years that anyone has been doing systematic research.”
The number of studies investigating post-treatment cognitive impairment has significantly increased in this decade. As science does a better job defining the difficulties stemming from chemobrain, many in the medical community have come to accept its existence.
A series of studies that combined neuropsychological testing with sophisticated brain imaging and molecular analyses allowed researchers to better define what was previously only loosely described through anecdotal evidence. And some research studies are beginning to yield new strategies to mitigate some of the quality-of-life impacts that can accompany cognitive decline after cancer therapy.
Consider a study of breast cancer survivors with persistent memory problems. Brain scans showed that the women who had received chemotherapy had a lower resting brain metabolism. While taking a memory test, the chemo-treated patients used a larger portion of their frontal cortexes than the untreated women. That meant that the treated women were working their brains harder to perform the task. Other imaging studies have found similar results.
In 2004, Syrjala and colleagues published findings from a first-ever, large-scale neuropsychological study that assessed stem cell transplant patients before and after treatment. They found significant reduction in cognitive function on all tests 80 days post-transplant. However, performance returned to pre-transplantation levels at one year on all measures except for grip strength and coordination. This year, Syrjala reported on the same group five years after treatment and found no difference between survivors and the regular population in executive function—high-level, multi-tasking abilities that influence more basic abilities like attention, memory and motor skills.
Interestingly, Syrjala found a higher percentage of patients than expected scored below average on tests for verbal fluency and memory even prior to their treatment. Other baseline studies of patients after diagnosis but before treatment have found this, too. The results suggest that blaming cognitive solely on chemotherapy is too limiting.
Researchers believe other factors associated with cancer, such as elevated levels of inflammatory cytokines—cell proteins that help regulate the intensity of the body’s immune response—and DNA damage, may contribute to below-average baseline cognition.
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Finding a common language
The growing interest in studying chemobrain has prompted researchers to better organize and standardize their efforts. The International Cognition and Cancer Task Force formed in 2006 to unite the global effort to study this problem. They found that scientists researching chemobrain around the world were using different tests and methods, measuring at different time points, and not surprisingly, finding different results. The group is working to set consistent measures to enable more apples-to-apples research comparisons.
“We need some common language even within the United States in how we’re doing the science so we can compare findings and know what is, in fact, a contradiction in findings versus a contradiction in methodology,” Syrjala said.
One of the central puzzles of chemobrain is that many of the symptoms can occur for reasons other than cancer treatment. Coexisting factors like age, fatigue, stress, as well as other medications, make it difficult to tease apart the driving contributors. Cognitive difficulties are also core symptoms for diagnosing depression and anxiety.
To better examine the aging issue, researchers are making efforts to include a greater number of older patients in studies of cognitive impairments related to cancer. According to a 2007 Institute of Medicine report on cancer in the elderly, 60 percent of all cancer survivors are older than 65; despite this, less than 20 percent of cognition studies included patients whose average age was older than 65. Though age is an independent risk factor for cognitive decline, sidestepping the issue does little to help oncologists advise their older patients about possible treatment side effects.
To address this disparity, Dr. Monique Cherrier, a University of Washington neuropsychologist, is conducting a study through the Seattle Cancer Care Alliance (the Hutchinson Center’s clinical treatment arm) to examine how hormone therapy for prostate cancer affects brain function. Since more than 70 percent of prostate cancer patients are over 65, Cherrier hopes to assess which cognitive difficulties are related to treatment versus aging.
Other researchers are turning their attention to mitigating cognitive problems. Some studies have shown modest improvement in memory problems among cancer survivors using a mild stimulant medication. Efforts are also being aimed at cognitive rehabilitation, coping strategies and adoption of healthy habits like exercise to improve working memory.
Overcoming the fog
Mark Giles has benefited from the intervention efforts of the Hutchinson Center and the University of Washington’s Department of Rehabilitation Medicine. Giles, whose stem cell transplant in 2000 put his acute myelogenous leukemia in remission, has struggled greatly with chemobrain. He’s had difficulty with fatigue, sustaining attention, recalling names, remembering faces, and learning new information.
His deficits and prolonged physical recovery left Giles unable to work and feeling despondent. “I kept saying, ‘I want to be a real boy again and get on with my life.’”
Giles has seen improvement with the passing of time and the ceasing of some of his medications. The 54-year-old joined “Survive and Thrive,” a strength and fitness program sponsored by the Center’s Survivorship Program and the YMCA, and found that physical activity helped a great deal. So did working with a rehabilitation specialist who helped him set goals and create routines.
Since numerous health and behavioral factors can affect optimal cognitive functioning, the first step for concerned cancer survivors is always to get an evaluation to determine if there are measurable deficits. Medications, nutrition and sleep patterns should be reviewed. Stress level and mood disorders should be assessed and, if necessary, treated. Depending on the severity of cognitive dysfunction, treatment may range from intervention by a work coach to the implementation of an aid such as a notebook or electronic device.
“We teach people to adapt and adjust expectations and scheduling so they do their most intensive brain work when they’re most alert,” Syrjala said. “There are lots of memory and organizing tools, too. And many people find building physical energy through exercise facilitates mental energy.”
Giles has taken many of these tips to heart. “Now I always pat my pockets for my keys, wallet and phone before I leave the house,” he said. “I keep a calendar, make lists, and allow myself some slack because I’m aware how easily distracted I am.”
Once an intensive-care nurse who thrived on rapidly changing medical technology and a demanding patient load, Giles recently renewed his nursing license. His goal: work and be of service to society once again.
He knows he is not alone. As the number of survivors continues to grow, cognitive deficits will become a critical quality-of-life concern for millions of cancer patients.And while it’s vital to research and address post-cancer cognitive issues, it’s also important to remember the big picture, Syrjala said: People facing these treatments are trying to save their lives.
“We weren’t worried about this 30 years ago because we were just trying very hard to keep people alive,” she said. “The best news is that we’ve made such progress that we can worry about these things now. It doesn’t make these concerns unimportant—they’re clearly important, and it’s essential for us to keep applying our scientific tools to the problem.”
Despite her memory problems, Miner hasn’t lost sight of her survivor status. “I was told I had six weeks to live without a transplant and today I’m in good health,” she said. “I have these few side effects, but they are definitely a small price to pay for getting past cancer.”