Can we train the chemo-brain?

“When I meet a friend on the street, I can’t even remember her name.”
“Where did I leave my keys?”
“Oh, darn I forgot my doctor’s appointment today!”

These phrases are not uncommon among cancer survivors suffering from “chemo-brain”.

Chemo-brain, cancer-brain, or more correctly termed cancer-related cognitive impairment (CRCI) or dysfunction (CRCD), refers to a change in cognitive functioning during and/or after treatment of cancer. The terms CRCI or CRCD were introduced, as these impairments were not solely related to chemotherapy. Surgery, radiotherapy and hormone therapy all seem to contribute to the development of CRCI. (Von Ah, 2015)

It is estimated that up to 75% of cancer patients experience cognitive dysfunctions during treatment, and 17%–35% patients experience more severe effects, even several years after the completion of treatment (Ahles et al., 2012). People suffering from CRCI have trouble with short-term memory, multi-tasking, complex problem solving, concentration, finding the right words, motor skills and mental efficiency. In breast cancer survivors changes in memory and attention were the most reported cognitive change (Green et al., 2019). These findings are similar with the cognitive complaints of cervical cancer survivors (Zeng et al., 2017). CRCI has a detrimental effect on quality of life (autonomy, return to work, social relationships, and self-confidence) in the sense of long-term care for cancer. As cancer survivorship improves, more patients are increasingly looking to receive support and guidance in this matter.

Psychological and sociodemographic variables like age, education level, intelligence, insomnia, obesity, physical activity, anxiety, depression and fatigue have been associated with CRCI. Also, factors related to the disease can have an effect on CRCI: disease site, cancer stage, comorbidities, treatment regimen, duration, concomitant therapies, cytokine levels, hormonal levels etc. (Myers, 2009). At last genetic factors – polymorphisms can predispose cancer survivors to CRCI (Lange et al., 2019).

The manifestation of these cognitive impairments is mostly subtle and scores on neuropsychological tests may be within normal limits. An explanation for this can be that cancer survivors may employ compensatory activation of additional brain regions to improve outcomes on neuropsychological tests, or that cognitive impairments generally affect activities of daily living, whereas neuropsychological testing is performed in a structured and distraction-free environment. Additionally, as there is no specific neuropsychological test for CRCI, it is hard to objectify the decrease in cognitive function in these patients.

The international cancer and cognition task force (ICTTF) recommends using cognitive tests with sufficient sensitivity to assess the cognitive domains that are mostly affected by cancer treatments. The Hopkins Verbal Learning Test-Revised, the Controlled Oral Word Association Test and Trail Making Test are the main measurements that the ICTTF recommends. With these measurements respectively verbal memory and delayed recall; speeded lexical fluency (generation of words); psychomotor speed (the ability to detect and respond to rapid changes in the environment) and executive function (working memory, flexible thinking, and self-control) can be assessed. (Lange et al., 2019)

Imaging of brain changes could provide more objective markers for CRCI, as brain imaging can show a reduction in grey matter volume or density, changes in brain activation, and alterations in white matter integrity in anterior/prefrontal regions. (Deprez et al., 2011)

CRCI management strategies have been studied, although high quality evidence is lacking.

A few modalities have been described to improve CRCI.

• Physical activity, or exercise can improve processing speed and reduce cognitive impairment. At this moment, no strong recommendations can be made on the amount, frequency and intensity of physical activity for the improvement of cognitive impairment. What is known is that physical activity improves quality of live, depression, sleep quality and recurrence and mortality rates (Rogers et al., 2017; Dieli-Conwright et al., 2018; Balhareth et al., 2019). Cancer survivors should be motivated to reach the recommended guidelines of The American College of Sports Medicine. Their guidelines for exercise call for 150 minutes of moderate or 75 minutes of vigorous aerobic activity per week, and 2 days per week of resistance training (e.g., with exercise bands or light weights) (Schwartz et al., 2017). However, when cancer survivors experience difficulties reaching these amounts of physical activity, they should be reminded that more is better but a little goes a long way!
• Cognitive rehabilitation, or cognitive behavioral therapy have been suggested to improve cognitive complaints, anxiety, depression and fatigue. However, the results are limited and mixed. Cognitive rehabilitation can comprise mindfulness, meditation, stress management and relaxation techniques.
• Pharmacological interventions are unsupported by existing evidence.

Fatigue and pain are also commonly described in cancer survivors and can have a detrimental effect on their quality of life. When cognitive impairments are added to fatigue and pain, returning to regular life and work after cancer treatment can be very difficult, especially in people with busy social life and high demanding work places.

In the light of treating the person in front of you within a bio-psycho-social framework, it is important for clinicians to firstly recognize these complaints in cancer survivors. Clinicians need to be aware of the possibilities to improve CRCI and further guide them along the long and curvy road of rehabilitation after cancer treatment. We recommend adding cognitive rehabilitation exercises to physical activity or exercise, to not only train the body but also train the “chemo-brain”.

Vincent Haenen

PhD Researcher at University of Antwerp and KU Leuven.

2020Pain in Motion

References and further reading:

Ahles, T., Root, J. and Ryan, E., 2012. Cancer- and Cancer Treatment–Associated Cognitive Change: An Update on the State of the Science. Journal of Clinical Oncology, 30(30), pp.3675-3686.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC36756...

Balhareth, A., Aldossary, M. and McNamara, D., 2019. Impact of physical activity and diet on colorectal cancer survivors’ quality of life: a systematic review. World Journal of Surgical Oncology, 17(1).
https://wjso.biomedcentral.com/articles/10.1186/s1...

De Groef, A., Devoogdt, N., Van der Gucht, E., Dams, L., Bernar, K., Godderis, L., Morlion, B., Moloney, N., Smeets, A., Van Wilgen, P. and Meeus, M., 2019. EduCan trial: study protocol for a randomised controlled trial on the effectiveness of pain neuroscience education after breast cancer surgery on pain, physical, emotional and work-related functioning. BMJ Open, 9(1), p.e025742.
https://pubmed.ncbi.nlm.nih.gov/30612114/

Deprez S, Amant F, Yigit R, Porke K, Verhoeven J, et al. 2011. Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. Hum. Brain Mapp. 32(3):480–93
https://pubmed.ncbi.nlm.nih.gov/29083464/

Dieli-Conwright, C., Courneya, K., Demark-Wahnefried, W., Sami, N., Lee, K., Sweeney, F., Stewart, C., Buchanan, T., Spicer, D., Tripathy, D., Bernstein, L. and Mortimer, J., 2018. Aerobic and resistance exercise improves physical fitness, bone health, and quality of life in overweight and obese breast cancer survivors: a randomized controlled trial. Breast Cancer Research, 20(1).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC61947...

Green, H., Mihuta, M., Ownsworth, T., Dhillon, H., Tefay, M., Sanmugarajah, J., Tuffaha, H., Ng, S. and Shum, D., 2019. Adaptations to cognitive problems reported by breast cancer survivors seeking cognitive rehabilitation: A qualitative study. Psycho-Oncology, 28(10), pp.2042-2048.
https://pubmed.ncbi.nlm.nih.gov/31364225/

Lange, M., Joly, F., Vardy, J., Ahles, T., Dubois, M., Tron, L., Winocur, G., De Ruiter, M. and Castel, H., 2019. Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors. Annals of Oncology, 30(12), pp.1925-1940.
https://www.annalsofoncology.org/article/S0923-753...

Myers, J., 2009. Chemotherapy-Related Cognitive Impairment. Clinical Journal of Oncology Nursing, 13(4), pp.413-421.
http://static.ons.org/Online-Courses/Psychosocial/...

Rogers, L., Courneya, K., Oster, R., Anton, P., Robbs, R., Forero, A. and Mcauley, E., 2017. Physical Activity and Sleep Quality in Breast Cancer Survivors. Medicine & Science in Sports & Exercise, 49(10), pp.2009-2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC56006...

Schwartz AL, de Heer HD, Bea JW., 2017. Initiating Exercise Interventions to Promote Wellness in Cancer Patients and Survivors. Oncology (Williston Park), 31(10):711-717.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC63615...

Von Ah, D., 2015. Cognitive Changes Associated With Cancer and Cancer Treatment: State of the Science. Clinical Journal of Oncology Nursing, 19(1), pp.47-56. https://www.researchgate.net/publication/272512586...

Zeng, Y., Cheng, A., Liu, X. and Chan, C., 2017. Title: Cervical cancer survivors’ perceived cognitive complaints and supportive care needs in mainland China: a qualitative study. BMJ Open, 7(6), p.e014078.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC55778...

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