More Than Chemo Brain: Several Factors Contribute to Cognitive Decline After Cancer

Though patients and survivors often complain of chemo brain during and after treatment for cancer, a growing body of research shows that there are multiple causes behind the cognitive decline many survivors experience.

Whatever the culprits, cognitive complaints persist for many cancer survivors long after their active treatment has ended, and there is increasing evidence to back this up, said Tim Ahles, in his presentation at the inaugural 2016 Cancer Survivorship Symposium.

Ahles, a behavioral psychologist at Memorial Sloan Kettering Cancer Center, noted that most of the research on the cognitive impact of cancer treatments has been done in breast cancer, with at least 20 longitudinal studies devoted to cognitive functioning in this population.

While almost everyone reports some temporary issues with cognitive function during their chemotherapy treatment, Ahles estimates that for about 15 to 20 percent of survivors, this condition may persist one or two years — for some even longer — though the research varies, with some studies finding no evidence of impairment and others reporting as much as 60 percent.

Advanced imaging techniques and animal studies have enabled researchers to better elucidate how exposure to chemotherapy can impact the brain, Ahles explained, and researchers theorize that the mechanisms may be a kind of “accelerated aging” that results in DNA damage, inflammation and increased oxidative stress, among other effects.

“If you think about it, what does chemotherapy do? What does radiation do? These affect all of these systems as well. There may be this complex interaction between specific effects of our cancer treatments and the impact on the underlying biology of aging.”

Among cancer survivors, we in the research community have traditionally called it ‘chemo brain,’ added Ahles. “Many of us started in this area believing that chemotherapy was the primary cause, but as it turns out, there’s growing evidence that endocrine therapies may also impact cognitive function … also hormone ablation therapy. Testosterone and estrogen are important in maintaining cognitive function, particularly working memory.”

Drawing a typical example of a woman with breast cancer, Ahles said, “she will have had one or maybe multiple surgeries with general anesthesia, chemotherapy, radiation, endocrine therapy — we really are studying that whole package of treatments.”

The most common cognitive issues individuals report after cancer treatment include problems with memory, concentration, and executive function, which for patients often translates into worry that they can’t multitask anymore and need to start over when they are interrupted or get distracted, explained Ahles.

Other frequent complaints, he said, involve a reduction in the ability to learn new material and reading comprehension, for example, survivors say they need to read articles two or three times to understand them. They may also report trouble working with numbers, for example, figuring out the tip at a restaurant. “People often tell me they feel like they’re in ‘a bit of a fog.’ “It’s not that they can’t learn; it just takes more effort and more time.”

Ahles stressed that when a survivor reports any loss of cognitive function, clinicians need to rule out other, potentially treatable, causes, such as sleep disorders (insomnia, sleep apnea), depression, anxiety, stress, pain (and any associated pain/sedating medications), as well as other comorbid conditions which can affect memory and cognition.

Certain genetic and other factors can make a patient more susceptible to cognitive impairment after treatment. Older age and a lower level of cognitive reserve, which Ahles explained involves not only IQ, but education, occupation, and cognitively-stimulating hobbies, can predict cognitive decline. Presence of the gene ApoE4 increases risk of Alzheimer’s disease, and, “it turns out if you’re E4 positive, you have an increased risk for cognitive decline secondary to any insult to the brain,” Ahles explained.

Moreover, although cancer treatment’s negative impacts on cognitive functioning have been studied predominantly in breast cancer, they have been reported in other settings as well, including adult survivors of childhood blood cancers.

What can be done?

“Unfortunately, we don’t have great treatments at this point,” Ahles told his audience, although a lot of work is being done.

In the area of pharmacologic interventions, he said, most are some variant of psychostimulants, for example, Ritalin (methylphenidate), Provigil (modafinil) and Aracept (donepezil). Ahles said that for some people, these agents can be very helpful, and from a clinical point of view, it can be determined within a very short period of time whether they are going to help or whether the individual’s quality of life is impacted by any side effects of taking them.

Preliminary research is under way in the area of cognitive rehabilitation in breast cancer survivors, Ahles said, including interventions aimed at memory and attention training delivered by rehabilitation psychologists or occupational therapists.

Investigators are also looking at the use of technology, including the effectiveness of computer-based interventions.

Ahles also pointed to evidence that exercise slows cognitive changes associated with aging:

“This makes a lot of sense. If you look at the literature on aging, probably the best thing one can do in terms of trying to slow cognitive aging is to exercise regularly. There are multiple side effects of cancer treatment, and exercise has an impact on multiple biologic systems, which may be why it works so well.”

Ahles said that as we await the results of ongoing studies looking at the role of exercise, it’s important to acknowledge that neurocognitive effects of cancer treatment can persist for a significant subgroup of survivors.

“The risk for cognitive problems is likely an interaction of various vulnerability factors, including age, cognitive reserve, genetics, lifestyle, environmental exposures — and our specific treatments.”

“It’s a very complicated interaction that we see, and obviously much more work on interventions is needed.”