Minds fixed on ‘chemo brain’
After years of being dismissed as a figment of patients’ imaginations or as a result of anxiety or depression, “chemo brain” is beginning to be taken seriously by cancer doctors and researchers.
The cognitive problems, such as trouble with thinking and memory, appear to be fairly common, affecting 16% to 40% of women undergoing chemotherapy for breast cancer, says Dr. Ian Tannock, chairman of medical oncology at the Princess Margaret Hospital in Toronto.
So far, most studies of “chemo brain” have been in women with breast cancer, but the problem can affect both sexes.
In one study by Tannock and others, women who had undergone chemotherapy for breast cancer fared worse, as a group, on certain cognitive tests than a similar group of women without cancer. The differences in cognitive functioning could not be explained by differences in age, education, menopausal status or mood.
Luckily, says Tannock, the problem is usually mild to moderate: “These women are not demented. It’s a subtle thing.” The problems usually improve after chemotherapy but in some cases may persist for years.
At the Netherlands Cancer Institute, researchers have conducted a number of studies suggesting that chemotherapy is linked to cognitive deficits. A 1998 study found cognitive impairment in 32% of women with breast cancer who were given high-dose chemotherapy and in 17% of patients getting standard-dose chemotherapy.
On average, the women were studied two years after treatment. Another Dutch study in 1999 also found that breast cancer patients who got chemotherapy had significantly more cognitive impairment than those who did not.
At Dartmouth-Hitchcock Medical School, psychologist Tim Ahles and his team studied 71 men and women who had had chemotherapy for lymphoma or breast cancer and 57 similar people who had received only surgery and localized radiation for those cancers. Five years after treatment, all were cancer-free, but those treated with chemotherapy fared worse on paper-and-pencil cognitive tests than those who did not get chemotherapy.
Still, “chemo brain” is tough to explain. At least until recently, it’s been thought that most drugs used in chemotherapy do not cross the blood-brain barrier, the protective membrane that acts as a filter between substances in the circulating blood and the brain. (One notable exception is the chemotherapy drug methotrexate when given in very high doses.)
Many chemotherapy drugs are too big or have chemical properties that prevent them from crossing the barrier, says Dr. Lawrence Shulman, chief medical officer at Boston’s Dana-Farber Cancer Institute. In fact, this is a major reason many chemotherapy drugs are ineffective at treating cancers that have spread to the brain.
But “chemo brain” could be caused by the drugs indirectly, in that they can cause the body to pump out natural chemicals called cytokines that do enter the brain and may trigger significant decreases in cognitive function.
Cancer cells themselves also pump out cytokines, says Christina Meyers, a professor of neuropsychology at the M.D. Anderson Cancer Center in Houston. That might explain why some cases of “chemo brain” seem to set in even before treatment starts, she says.
And some cognitive problems experienced by cancer patients might be caused by drugs given along with chemotherapy, such as anti-nausea medications, steroids, sedatives and antihistamines.
Rachel Morello-Frosch, 37, an assistant professor of environmental studies at Brown University who had chemotherapy for breast cancer 10 years ago while she was in graduate school, never could figure out what caused her “chemo brain.” Yet for three or four days after every treatment, she would “have a conversation with someone and completely forget what they said,” she says.
Part of the problem of understanding “chemo brain” is that definitive, long-term tests -- on the same patients before, during and after chemotherapy -- have not been done, says Cheri Geckler, a neuropsychologist at Tufts-New England Medical Center.
Another part is that it’s been difficult to determine, at least in women with breast cancer, whether “chemo brain” comes from chemotherapy or from the fact that chemotherapy plunges some women into abrupt menopause, which can cause hormonal, mood and sleep disturbances.
And “none of these studies has been done in large enough numbers or with good enough controls for us to be certain of what’s going on,” says Dr. John Glaspy, an oncologist at the Jonsson Comprehensive Cancer Center at UCLA.
Potential treatments for “chemo brain” are at an even earlier stage. Researchers are considering drugs used to treat Alzheimer’s disease, stimulants, drugs used to treat anemia and the related fatigue that can lead to some cognitive impairment.
