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SCIENCE & TECHNOLOGY FIGHTING Melanie Orndoff receives chemotherapy for leukemia.
CANCER'S TOLL ON THE BRAIN Chemotherapy may impair cognitive abilities, but remedies are under development
Known informally as chemobrain or chemofog, this condition can make it hard to find the right word during a con versation or to learn new material. People suffering from chemobrain may "have to read the same page of material over and over again," according to Tim A. Ahles, a psychologist who is a professor of psychia try and program director of the Center for Psycho-Oncology Research at Dart mouth Medical School. They may have difficulty finding their keys or remember ing what they meant to buy at a store. The speed at which they process information may drop. Compared with the cognitive effects of conditions such as Alzheimer's disease, Ahles notes, the mental changes accom panying chemobrain "are relatively subtle. But they still can be very disruptive and interfere with achieving work or educa tional goals." The changes that characterize chemo brain have proven hard to spot in standard ized tests of memory and attention. Pa tients who experience cognitive changes after chemotherapy often score in the nor-
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SOPHIE L. ROVNER, C&EN WASHINGTON
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OCH, H E N SHE WAS TREATED
for breast cancer in 2003, Janet B. suffered the typi cal side effects of chemo therapy: nausea, fatigue, and hair loss. Subsequent radiation treat ments barely fazed her, apart from causing some additional fatigue. But after her cancer treatment ended, when she was struggling to regain her strength, she no ticed another problem. Her short-term memory was shot. "I'd always been a little absent-minded," she says, "but that got a lot worse. If I start a load of laundry and the phone rings, I'll forget I was doing laundry and I'll go do something else." Janet also finds it harder to concentrate now. "I'm more distractible," she explains. "It's like suddenly I have attention deficit disorder." Janet's sense of direction is no longer re
liable. Nor can she plot a driving route in her head anymore. "Sometimes when driv ing in a familiar area, I get a little disori ented and can't visualize what landmarks are coming next," she says. "It's not like I'm totally lost, but I have to think about it more." Despite the side effects,Janet is delight ed with the success ofher cancer treatment. But patients, physicians, and biomedical researchers are increasingly asking what price patients pay for beating cancer with this type of treatment. Chemotherapy, though life-saving, may itself cause cancer later in life. The treat ment may also cause other persistent prob lems such as hearing loss, heart damage, and infertility. And evidence is building that chemotherapy can lead to difficulties with memory and concentration, much like those Janet has experienced.
DUAL PURPOSE Ritalin, which is typically used to treat attention deficit hyperactivity disorder, might also have some utility in chemobrain cases.
mal range in these tests. Unfortunately, such tests are usually administered only after chemotherapy treatment, so changes in an individual's test results are rarely de termined. Even when pretreatment tests are conducted, however, it's not easy to in terpret the results because the period prior to treatment is so stressful. Christina A. Meyers, a neuropsycholo gist at the University of Texas M. D. An derson Cancer Center, is one of the few
'If we can understand the cause of chemobrain, then hopefully we can come up with ways of either treating it or, ideally, preventing the problem/' WWW.CEN-0NLINE.ORG
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SCIENCE & TECHNOLOGY researchers who have collected data on patients prior to treatment. She has found evidence that patients with hematologic, lung, or breast cancer showed learning and memory problems before starting chemotherapy. Among the breast cancer patients, che motherapy nearly doubled the pretreatment percentage of patients suffering from cogni tive difficulties, though half of them improved within a year of treatment.
another workshop speaker. Fleishman is director of cancer supportive services at Continuum Cancer Centers ofNew York: Beth Israel Medical Center. Hormonal changes that can occur with cancer or its treatment can also play a role, he added. As breast cancer patientJa net, who was 51 when she had cancer treatment two years ago, sums it up: "I can see lots of differences in cognitive processes since chemo. It's hard to know what is chemo related and what is just to be IT'S POSSIBLE that an in expected at this age." flammatory immune response caused by cancer itself and/or Whatever the basis for by cancer treatment may be re their cognitive difficulties, sponsible for some of these cas most patients report a grad es of chemobrain, according to ual improvement within six Meyers. The immune system is months to a year or two after regulated by proteins known as treatment. "However, there is cytokines, which are secreted agroup ofpeople who say they by immune cells. Cytokines are improve to a certain extent activated in response to infec and then hit aplateau and nev tion or injury and cause brainer improve after that," Ahles mediated symptoms, including SYMPATHETIC Although the cognitive changes wrought says. "We don't know how big fatigue, lack of motivation and by chemobrain aren't as severe as those in Alzheimer's that group is, but it's probably appetite, sleep disturbance, and patients, Ahles says, they can nevertheless interfere with in the 20-25% range." problems with concentration. work and educational goals. Furthermore, the source of "Certain cancers and cancer their ongoing cognitive prob treatments secrete or induce cytokines, Several other factors can contribute to lems is uncertain. Chemotherapy may af which may be one mechanism by which cognitive difficulties experienced by che- fect the brain directly, or it may alter some cancer-related symptoms, including cogni motherapypatients.Duringchemotherapy other aspect ofhuman biology. "Those are tive impairment, develop," Meyers says. and shortly thereafter, "almost everybody the kinds of things that we are intensively For instance, Meyers found that pa reports having problems with memory and trying to study right now," Ahles says. "If tients with acute leukemia had elevated concentration," Ahles says. Patients are we can understand the cause of chemo levels of certain cytokines circulating in "anemic, they're nauseous, they're taking brain, then hopefully we can come up with their blood, which correlated with the ex medications that are sedating, and they're ways of either treating it or, ideally, pre tent of their cognitive impairment and fa not sleeping well. There's a whole lot of venting the problem." tigue. This finding lends some support to reasons why they could be experiencing One fundamental question that needs the hypothesis that chemobrain may be cognitive problems." to be answered is whether chemotherapy due at least in part to cytokine activation Some people continue to experience fa drugs get into the brain. Traditionally, pas of the immune system, Meyers says. Con tigue or sleep disruption after chemother sage of chemotherapy drugs into the brain ceivably, anti-inflammatory drugs might apy. Others battle depression and anxiety. was believed to be blocked by the bloodbe useful as an antidote to the harmful Some patients continue to take medica brain barrier, according to the Mayo Clin tion after chemotherapy, either ic. But some researchers now suspect that to hold cancer at bay or to treat some of these drugs slip past. other conditions. "If you treat Once they're in the brain, chemothera the fatigue or depression or you py drugs could cause atrophy of gray mat change the dose of a sedating ter and demyelination of white matter fi medication, very often the cog bers, Ahles says. The compounds may also Carmustine Cisplatin nitive problems will resolve," alter neurotransmitter levels. Ahles said during a June 2004 NEUROTOXIC Chemotherapy agents workshop on chemobrain. The ANOTHER HYPOTHESIS is that chemo carmustine and cisplatin—along with workshop was hosted by Cancer- therapy drugs cause vascular injury in the methotrexate and cytarabine—can damage Care, an organization that pro brain and perhaps elsewhere. It's also pos myelin in the brain. vides counseling and educational sible that the free radicals produced by che services related to cancer. motherapy to kill cancer cells also harm Other potentially reversible sources of membranes and DNA of normal cells. activity of cytokines, she adds. Cytokine There are still many unknowns, ac antagonists—-which prevent the binding cognitive problems include vitamin B-12 of cytokines to their target cells in the and folic acid deficiency or an underactive cording to the Mayo Clinic. Which che immune system and elsewhere—are un- thyroid, according to Stewart Fleishman, motherapy drugs are more likely to cause 34
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der development and may also help. Such treatments would have to be used with cau tion so as not to suppress beneficial im mune activity.
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