June 13, 2003

Researchers hope to lift fog associated with chemotherapy in some cancer patients

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Researchers hope to lift fog associated
with chemotherapy in some cancer patients

“Chemo-brain” or “chemo-fog,” a phenomenon experienced by some cancer patients who undergo chemotherapy, has been misunderstood for years. The fog may soon be lifting though, and the problems may be considered more than a phenomenon, as a professor in Psychiatry looks to offer scientific answers to some of the cloudy questions.

Laurel Brown, Ph.D., assistant professor of Psychiatry, is the principal investigator of a pilot study currently under way at the Vanderbilt Ingram Cancer Center, in conjunction with the departments of Psychiatry and Psychology.

Brown is looking to uncover some of the problems many breast cancer patients experience after being treated with chemotherapy, and the cause of those problems. Patients who are affected by “chemo brain” typically report memory problems and problems with mental clarity and focus. Some patients report only mild problems, while others feel significantly impaired.

Brown says previous studies indicate that roughly 30 percent of patients who undergo chemotherapy report cognitive deficits. She theorizes that the problems may be related to damage to a specific region in the brain during treatment. “The hippocampus plays a critical role in learning and memory, especially declarative memory,” said Brown.

Declarative memory involves explicit information about facts, like remembering your phone number or the names of friends.

“It is different from procedural memory, which is the kind of memory that stores information like how to ride a bike or how to play the piano. It is what we know consciously or factually,” Brown said.

Declarative memory often involves associations with other events and other areas of the brain, but it relies heavily on the hippocampus. “We know that the hippocampus is vital for declarative memory and the hippocampus is especially vulnerable to damage from sources experienced by breast cancer patients — such as dexamethasone, chemotherapeutic agents, or simply high levels of endogenous glucocorticoids that are common during stressful situations,” she said.

Breast cancer patients are commonly treated with a steroid known as dexamethasone or decadron to curb some of the side effects of chemotherapy. But in theory, Brown says it might be contributing to the problems known as “chemo brain.”

Pam Severy of Brentwood, Tenn., had a modified radical mastectomy and breast reconstruction in January 1999. She doesn’t know if she had dexamethasone, but she thinks her problems today are related to “chemo brain.” “I really don’t know what is affecting me, but something has.”

She began to notice problems when she went back to work. “I didn’t work for five months during treatment. I went back part-time at first, and I would go in and I couldn’t remember my password to get into my computer, and I just sat and bawled. I knew I knew it and I just couldn’t remember. That just tore me up, and I still have that problem.”

Dr. Barbara Murphy, associate professor of Medicine and director of the Pain and Symptom Management Research Program at VICC, says there are some known risks to dexamethasone and other steroids given during chemotherapy, but it’s hard for health care providers to offer warnings about the role of steroids in “chemo brain” because too little is still known about it.

“Does prolonged treatment with corticosteroids cause medical problems? Sure it does, no doubt about it. But most cancer patients aren’t on prolonged steroids,” Murphy said. “The relative role of steroids in ‘chemo brain’ is unknown. Other drugs may be contributing. It is important for us to know what is causing ‘chemo brain’ so that we can make intelligent decisions about relative risks and benefits.”

Brown’s study will enroll women after they have been diagnosed with breast cancer, but before they have been treated to see what, if any problems can be directly related to treatment.

She plans to measure deficits in declarative memory using The Randt Memory Test and The Benton Visual Retention Test, hippocampal volume loss and hippocampal functioning will be tested using structural and functional MRI, and changes in the daily fluctuation of cortisol levels will be noted. All three will be measured before and after treatment for breast cancer.

Brown hopes to gather evidence to support her theory that the problems known as “chemo brain” are related to damage in the hippocampus. She hopes eventually to understand the phenomenon well enough to be able to predict which patients might develop these problems during chemotherapy.

“If we could learn how to predict which patients might be at an increased risk for cognitive changes, then perhaps their treatment could be tailored to try to avoid the development of memory problems,” said Brown.

She added that for those patients who do experience problems, in the meantime, there are coping techniques and memory aids that can help. Brown also says that there is new research suggesting that “chemo brain” is not permanent and that the hippocampus may regenerate itself after damage or loss.

“A few years ago we thought once you lost brain cells they were gone for good. Now there is strong evidence that, especially in the hippocampus, new cells can be reformed well into old age,” said Brown.

For more information about the study, call Brown at 343-2131, or Barbee Smith at 322-0387.