With the number of cancer survivors in the United States at nearly 14 million according to the National Cancer Institute and cancer survivors living longer than ever, researchers are increasingly studying the long-term side effects of cancer and its treatments. One of those side effects is cognitive change — including problems with memory and concentration. Cognitive changes can significantly diminish a person’s quality of life after cancer treatment.
An article by a team of Memorial Sloan Kettering investigators, published in October in the Journal of Clinical Oncology, examines what is known about the causes and effects of these cognitive problems and reviews the current “state of the science” in this growing field.
Tim A. Ahles, a Memorial Sloan Kettering behavioral psychologist and the article’s lead author, spoke about what researchers found in a recent interview.
How common are cognitive changes?
It’s not uncommon at all for people to experience cognitive difficulties when they’re in active treatment for cancer. There are a lot of reasons for that: They don’t feel well, they’re tired, they’re anemic, and they may be taking sedative medications. The majority of patients in the middle of treatment report issues such as loss of short-term memory, difficulty concentrating, and inability to multitask.
Recovery happens slowly, but following treatment, most people do report improvements. About a year after treatment, between 75 and 80 percent say that their cognitive function is back to normal.(1)
Although most people recover, there are still millions of survivors whose cognitive function may never completely return to what it was before cancer. These deficits might affect someone’s ability to return to work or complete their education, and they can impact quality of life in many other ways.
The problems you’re talking about are often called “chemobrain,” but are they caused only by chemotherapy?
No. If you look at the typical treatment for breast cancer, for example, it involves at least one surgery with general anesthesia, and also chemotherapy, radiation therapy, and hormone therapy. So when we say we’re studying the effects of cancer treatment, we’re really looking at the whole package. We’re not able to separate out one component of the treatment from the others.
We know that estrogen is important for memory function in women, so it makes sense that breast cancer patients who are treated with drugs that affect estrogen levels, such as tamoxifen and aromatase inhibitors, are likely to have problems with memory. In the same way, testosterone is critical for cognitive function in men, and men with prostate cancer who are given hormone-blocking drugs commonly have cognitive difficulties.
Of course, for patients with brain tumors, problems can also be caused by the location of the tumors themselves, and by surgery and radiation treatments in areas of the brain that may directly influence these functions.
How do cancer treatments affect the brain?
That’s something we’re still figuring out. Most chemotherapy drugs do not cross the blood-brain barrier, but some do, so there may be some direct effects on the brain. Even if they don’t cross the barrier, the drugs may cause something called oxidative stress. This process creates molecules called reactive oxygen species that do cross the barrier and can be toxic to the brain.
Most chemotherapy drugs damage DNA, and we know that the accumulation of DNA damage can lead to changes in the brain. Chemotherapy also triggers the production of cytokines, small signaling molecules that can have an effect on the immune system and other regulatory systems in the body.
We’re also considering the effects of radiation therapy, even if it’s not administered near the brain. Like chemotherapy, radiation can damage DNA and cause changes in the immune system.
What studies are being done to learn about the relationship between cancer treatments and cognitive change?
One area that’s very important is brain imaging. A number of studies have shown actual changes in brain structure and function in patients following cancer treatment. We have an imaging study going on now that follows breast cancer patients throughout treatment. We image their brains before treatment and then again during and after treatment to try to pinpoint when and where changes are occurring.
Animal models are also useful because we can give each treatment separately to sort out the effects that each one has independently on the brain.
Because much of the research in this area has been done in breast cancer patients, we are also expanding into other types of cancer, especially those that affect men and women equally. We and others have done research in lymphoma, and there is a group in Australia studying patients with colorectal cancer.
Finally, we need to do more to understand the cognitive effects of cancer treatment within the context of aging. Aging naturally reduces cognitive function, particularly memory and concentration, so it makes sense that age might make some people more vulnerable to long-term changes. So far, much of the research has been done in younger cancer patients, and we’re trying to get more data on adults aged 60 and above.
What has research taught us about how we can treat or prevent these problems?
There are two main approaches right now. One is related to medication, looking at stimulant drugs like methylphenidate (Ritalin®) and modafinil (Provigil®). There is evidence that these drugs are effective for some people.
The other approach is developing more cognitive interventions, where people are taught new skills and ways that they can compensate for their deficits. Elizabeth Ryan, a neuropsychologist at Memorial Sloan Kettering and one of the coauthors on our paper, is looking at computer-based methods for treating cognitive problems in breast cancer patients.
Unfortunately we don’t know enough yet to be able to prevent cognitive problems from occurring, and this is a big part of why research is so important.
What services are available for cancer patients experiencing cognitive changes?
Specialists on our Neuropsychology Service can perform cognitive testing to assess your cognitive skills and symptoms, help clarify the most likely cause of cognitive changes, and recommend tactics for coping with changes.