Wednesday, August 12, 2009

The Fog That Follows Chemotherapy

Published: August 3, 2009

As more people with cancer survive and try to return to their former lives, a side effect of chemotherapy is getting more and more attention. Its name is apt, if unappealing: chemo brain.

Nearly every chemotherapy patient experiences short-term problems with memory and concentration. But about 15 percent suffer prolonged effects of what is known medically as chemotherapy-induced cognitive impairment.

The symptoms are remarkably consistent: a mental fogginess that may include problems with memory, word retrieval, concentration, processing numbers, following instructions, multitasking and setting priorities.

In those affected — and doctors at this point have no way of predicting who might be — it is as if the cognitive portion of the brain were barely functioning. Symptoms are most apparent to high-functioning individuals used to juggling the demands of complex jobs or demanding home lives, or both.

The chemo brain phenomenon was described two years ago in The New York Times by Jane Gross, who noted that after years of medical denial, “there is now widespread acknowledgment that patients with cognitive symptoms are not imagining things.”

Some therapists have attributed the symptoms of chemo brain to anxiety, depression, stress, fatigue and fear rather than direct effects of chemotherapy on the brain and hormone balance. Yet when such factors dissipate, the symptoms may not. Recent studies that took other influences into account and analyzed how patients’ brains worked before and after cancer treatment have shown that cognitive effects of chemotherapy are real and, for some, long-lasting.

There are now two new books on the subject: “Chemobrain” (Prometheus Books), by Ellen Clegg, an editor at The Boston Globe, and “Your Brain After Chemo” (Da Capo Press), by Dr. Daniel H. Silverman, a leading researcher in the field, and Idelle Davidson, a health journalist and former breast cancer patient. Dr. Silverman heads the neuronuclear imaging section at the University of California, Los Angeles, Medical Center.

Ms. Clegg’s book, the more technical of the two, delves into details of research and may confuse readers about the validity of her subtitle, “How Cancer Therapies Can Affect Your Mind.” The more user-friendly book by Dr. Silverman and Ms. Davidson, subtitled “A Practical Guide to Lifting the Fog and Getting Back Your Focus,” acknowledges the controversy but cites both anecdotal and research reports showing that the problem exists independent of other factors that can beset cancer patients.

One Woman’s Symptoms

Barbara D. Wick, an insurance consultant in the Chicago suburbs who has been in and out of treatment for ovarian cancer for six years, says her cognitive problems have subsided somewhat since her last round of chemotherapy ended six months ago. Among the symptoms she experienced were these:

Inability to focus on anything with any complexity or depth.

Inability to retain information, especially names.

Difficulty retrieving words and substituting wrong words (“chicken” for “kitchen”).

Difficulty analyzing anything other than simple questions.

Inability to follow instructions when cooking or knitting, for example.

In their book, Dr. Silverman and Ms. Davidson quote a photographer treated for breast cancer at age 34, who said: “Task completion is where I’m most affected cognitively. It’s as if the follow-through feature has been removed from my brain.”

Another patient, Patrick, a diagnostic radiologist treated for non-Hodgkin’s lymphoma at age 58, had to quit his job when he realized he was making mistakes. “I would lose my place and have to go back and start over with an exam,” he said. “I tried to explain a procedure to a patient and I got very confused.”

At the supermarket, Patrick and his wife put groceries in the car, then he drove off without her. He forgot pots on the stove until the smoke detector went off. Upset by the loss of his former self, he contemplated suicide. After psychiatric treatment, the depression lifted, but the confusion did not.

Searching for the Causes

It is not yet clear what happens during cancer treatment to cause symptoms of chemo brain. Some experts think some anticancer drugs could have direct toxic effects on neurons, although most drugs do not penetrate the blood-brain barrier. Some evidence from animal and human studies suggests that cancer treatment can cause biochemical or anatomical changes in the brain, or both.

Dr. Silverman reports that metabolic imaging studies have shown that “people exposed to chemotherapy have impaired brain function in certain regions compared to others who have not been exposed.”

Tim Ahles, director of neurocognitive research at Memorial Sloan-Kettering Cancer Center in New York, is looking into a possible relationship between chemotherapy-induced cognitive changes and DNA damage in breast cancer survivors.

Several symptoms of chemo brain resemble effects of estrogen loss after menopause caused by surgery. Since treatments for breast and ovarian cancers can suppress the production or action of estrogen, loss of estrogen may account in part for chemo brain in women.

Among women past menopause treated with an aromatase inhibitor that prevents the body from making estrogen or with tamoxifen, which blocks the action of estrogen on breast cancer cells, those on the aromatase inhibitor, which results in much lower levels of estrogen, “had significantly poorer performance on learning and memory measures,” Pauline M. Maki of the University of Illinois in Chicago reported.

Hormonal changes can also occur in men undergoing cancer therapy. In a study of men with prostate cancer treated with drugs that depleted androgens, treatment with an estrogen improved their performance on memory tests.

Controlling for brain function before cancer treatment begins can help determine cause and effect. In one study, cancer patients took a battery of neuropsychological tests before starting chemotherapy, three weeks after completing treatment, and again one year later. Although a third of the patients had signs of cognitive impairment before therapy began, the number jumped to 61 percent after treatment, and half remained impaired a year later.

This is the first of two columns on cognitive problems from chemotherapy. Next week: coping with the effects of chemo brain.

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