Chemobrain: Research the Nurse Can Apply

Jill Shelton, RN, BSN

As nurses, we are often in a unique position to detect subtle changes in our patients, ones that cannot be seen on a monitor or gleaned from an office visit. A slight change in behavior or mood can indicate a problem under the surface, and perhaps nowhere is this more applicable than in our ability to detect signals of chemotherapy-induced cognitive impairment (CICI), also known as “chemobrain.” We must diligently listen to our patients, validate their concerns, and provide strategies they can apply.

To be effective in this endeavor, nurses must stay current with the research and recommendations, with an eye toward understanding possible causes, treatment strategies, and most importantly, learning how we can best support these patients.

Assessing Chemobrain

With symptoms such as short-term memory loss, difficulty multitasking, and impaired thinking, CICI can be accompanied by commonly associated conditions like fatigue, insomnia, and depression. The research shows that patient concerns most commonly involve learning and memory, processing speed, verbal and spatial abilities, and problems with executive function (eg, planning and decision making).^1,2

A validated assessment tool for CICI has not yet been established. Neuroimaging has been used in the setting of studies or clinical trials but is not a cost-effective option.² An MRI may reveal decreased integrity and volume of cerebral gray and white matter, as well as structural and functional changes that correlate with complaints of cognitive decline.^1,3

Neuropsychological testing is time consuming for patients and requires special training to administer. Self-reporting of cognitive decline by patients, although difficult to quantify, still provides important data that indicate what the patient is experiencing and whether there has been improvement.²

Functional MRIs have been used to assess brain activity while performing tasks. Susan Krigel, PhD, a licensed clinical psychologist with the Midwest Cancer Alliance, described a 2007 study by Ferguson et al involving 60-year-old twins—one who had had chemotherapy and one who hadn’t—and each was asked to perform tasks during a functional MRI. For the woman who had chemotherapy, more parts of her brain were seen to be working at the same task, suggesting areas of hyperactivity that may demonstrate deficits.⁴

“There has also been some thought as time has gone on, that areas of hypoactivity are also indicative of problems,” Krigel explained. “Even at rest, there are differences in what the brain is doing … people who’ve had chemotherapy, whose brains are really active, they’re kind of ping-ponging around as if they have attention deficit disorder.”

Possible Causes of Chemobrain

Merriman et al proposed a model suggesting that the combination of cancer treatment and clinical factors results in changes to regulation of hormones, neurotransmitters, and cytokines. In combination with age and genetics, this leads to cognitive changes.⁵ Fardell et al proposed a model suggesting that “chemotherapy increases inflammation and oxidative stress and decreases brain vascularization, neurogenesis, growth factors, and catecholamines,” leading to impaired memory and learning.⁶

Genetic predisposition

Arash and Myers note that variants of genes encoded with apolipoprotein E (APOE), which is involved in repairing the brain after injury, and catechol-O-methyltransferase (COMT), which participates in the breakdown of catecholamines, are associated with age-related decline. The “accelerated aging hypothesis” suggests that cancer treatment speeds up the aging process through multiple channels (ie, inflammation, DNA damage) and individual patients may be susceptible to a certain channel.²

Direct neurotoxicity

While we know that certain chemotherapy drugs are especially neurotoxic, it can be difficult to differentiate them when multiple agents are used in combination, in addition to radiation or surgery.²

Inflammation

Systemic inflammation from chemotherapy and other treatments such as radiation, surgery, and biologic therapy is another possible cause. Studies show that circulating pro-inflammatory cytokines impair memory in animals and, when administered to the brain, increase use of neurotransmitters that are critical to sleep, memory, and mood.²

Treatment Options and the Nurse’s Role

Pharmacologic

Vitamin E shows some promise of improvement in verbal and visual memory while gingko biloba has not demonstrated cognitive improvement. Neurostimulants such as modafinil, FDA approved for treatment of narcolepsy, and methylphenidate, approved to treat ADHD, have been evaluated in small studies for cancer-related cognitive changes, but results have been mixed.²

Nonpharmacologic

Exercise is encouraged because of its ability to reduce inflammation and fight fatigue. Meditation, yoga, aerobic, and strength training are shown to have an impact, noted Krigel.

“With insomnia, anxiety, and depression, exercise helps.” For patients and survivors who are reluctant or say they don’t like to exercise, she suggested helping them find some activity they do like. Studies are under way to evaluate the impact of Qigong, a Chinese practice of physical and breathing exercises to determine whether it is the movement, the combination of movement and sound, or the support of being with others, that may be effective.

Cognitive training has been noted as likely to be effective, but the evidence around cognitive rehabilitation and behavioral training requires further study.²

Psychoeducation is also being studied, Krigel noted, for example, a 6-week intervention providing information on sleep, anxiety, depression, diet, exercise, and helping individuals learn about memory and strategies to improve their memory. Researchers are looking to see if such an approach can have an impact on patients’ level of perceived impairment and whether that impact persists.

“Nurses are in a great position to be able to help people figure out priorities because they know comorbidities,” advised Krigel. “Is this an anxious person? Are they depressed? How’s their sleep? Set priorities, help people figure out what the biggest priority is and start working with that, and keep touching base with them over time.”

Finally, Krigel suggested encouraging patients and survivors to try compensatory strategies, such as organizing with calendars, alerts, reminders, lists, and routines—these all can be helpful. Asking for help, practicing patience when forgetful, and acceptance of the situation are other strategies that may be helpful but take time.

Additional Resources

The advocacy group cancercare fact sheet “Coping With Chemobrain: Keeping Your Memory Sharp” is a helpful patient education resource offering practical tips you can share with patients and survivors.

References

1. Krigel S. Series: Part 1: Chemobrain: It's Real, It's Complex, and the Science Is Still Evolving; Part 2: The Science Behind Chemobrain; Part 3: Patient Recommendations for Chemobrain. http://bit.ly/2dayEUs. Accessed September 28, 2016.
2. Arash A, Myers JS. The effect of cancer treatment on cognitive function. Clin Adv Hematol Oncol. 2015;13(7):441-450.
3. Natori A, Ogata T, Yamauchi, H. (2016). A piece of the ‘chemobrain’ puzzle: pNF-H. Aging. 2015;7(5):290-291.
4. Ferguson RJ, McDonald BC, Saykin AJ, et al. Brain structure and function differences in monozygotic twins: Possible effects of breast cancer chemotherapy. J Clin Oncol. 2007;25:3866-3870.
5. Merriman JD, Von Ah D, Miaskowski C, et al: Proposed mechanisms for cancer- and treatment-related cognitive changes. Sem Oncol Nursing. 2013;29:260-269.
6. Fardel JE, Varcy J, Johnston IN, et al: Chemotherapy and cognitive impairment: Treatment options. Clin Pharmacol Ther. 2011;90:366-376

Jill Shelton, RN, BSN, is a clinical manager for Outpatient Neurosciences at Vanderbilt Medical Center.