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Can "chemobrain" be mitigated?

Have you ever locked your keys in the car? Forgotten an appointment? Sure, everyone has memory lapses from time to time. But for some cancer patients who undergo chemotherapy, such slips happen all too often. "Chemobrain," as patients call the condition, is characterized by memory problems, trouble concentrating or multitasking, and difficulty summoning the right word in conversation.

Persist: "For some people these are acute side effects of the treatment, and for some people these side effects actually persist long after the treatment," says Tim Ahles, Ph.D. The director of DMS's Center for Psycho-Oncology Research, Ahles studies the effects of chemotherapy on long-term cognitive function. "We are very interested in why some people have these long-term cognitive defects," he says. He and his collaborators want to know what factors make some patients more vulnerable to these effects than others.

Currently, the researchers are assessing

the cognitive function of patients with lymphoma and breast cancer, both pretreatment and posttreatment. They are then evaluating associations between the development of long-term cognitive defects and several other variables. The variables they are looking at include the types and doses of chemotherapy the patients have received and the genetic differences among the individuals. For example, are patients who receive a particular regimen of chemotherapy more likely to develop long-term cognitive defects? Or is there a particular gene that triggers vulnerability to these side effects?

One particular gene the group is examining is called APOE. One version, or allele, of this gene, E4, has been associated with Alzheimer's disease and traumatic brain injury. Recent research by Ahles's team suggests that the carriers of APOE's E4 allele may have a higher risk of developing long-term cognitive defects after receiving chemotherapy.

Side effects: Most patients who experience chemo-related cognitive

defects find that they return to normal shortly after they finish their regimen, but "for some people these side effects actually persist long after the treatment," explains Ahles. His group has published data showing that lymphoma and breast cancer survivors who received chemotherapy experience more cognitive defects five years after the conclusion of their treatment than do similar patients who received only nonsystemic treatment, such as surgery or local radiation.

Chemotherapy confers an increased chance of survival, of course, as well as an increased risk of cognitive defects. But these problems do affect long-term quality of life for some patients. Could it one day be possible to get the benefit without the risk? Ahles and his colleagues hope so. Their ultimate goal is not just measuring the problem but mitigating it. "If we really understood the mechanism," he says, "there will hopefully be drug interventions that may either prevent or reduce the negative cognitive impact of chemotherapy."

Kristen Garner

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