Time to talk about "chemobrain"

Neurocognitive Dysfunction

Diagnosis, prevention, treatment, and recovery

Cancer Patients & Cancer Survivors


Neurocognitive dysfunction (AKA “chemo brain”, “chemo fog”), resulting from cancer treatment, is now a recognized biomarker reflecting treatment effects, disease status, and psychological well-being.

Recent reports suggest that up to 75% of cancer patients may experience subtle cognitive changes that make day-to-day management of work and family responsibilities very difficult. Moreover, debilitating neurocognitive dysfunctions are reported by 15% to 50% of cancer patients treated with chemotherapy.

Cognitive domains disrupted by neurocognitive dysfunction include:

  • Attention

  • Executive function

  • Language

  • Memory

  • Processing speed

  • Verbal learning

Etiology of Disease

Functional MRI studies have documented that cerebral functional and structural changes correlate with complaints regarding impaired cognition and performance, and these alterations persist over time.

There are multiple hypotheses for brain changes that underlie neurocognitive impairment, resulting from cancer treatment including disruption of hippocampal cell proliferation and neurogenesis, chronic inflammation, oxidative stress,, white matter disruption,, changes in cerebral blood flow, and metabolism.  

For instance, treatment with tamoxifen has been associated with functional declines in verbal learning, memory, and executive function, when compared with treatment using exemestane. The biologic basis for tamoxifen related neurocognitive dysfunction may be associated to estrogen receptors in the hippocampus and prefrontal cortex that initiate intracellular signal transduction pathways and induce spinogenesis and synaptogenesis.

Additional factors currently being studied include age, hormonal status, baseline cognitive performance, educational level, genetic predisposition, depression, anxiety, fatigue, pain, anemia, time since treatment, and dietary factors.

Diagnostic Evaluations

More than thirty diagnostics are currently suggested to improve pathogenic understanding of neurocognitive impairment. While these diagnostics may provide further insight into the etiology of an individual’s neurocognitive impairment, NCCN guidelines state these tests are not warranted without first deploying a neuropsychological evaluation.

TREATMENT (follows NCCN Guidelines)

Neurocognitive impairment, related to cancer treatment, is a rapidly evolving field of medical science. A review of the literature reveals four evidence-based, non-invasive, low-cost interventions that can improve cognitive function and quality of life.


A randomized controlled trial assessing the efficacy of modafinil for fatigue and cognitive function in breast cancer survivors found significantly greater improvement in memory and attention among patients receiving modafinil than in a placebo group (18).  Additionally, donepezil was found to enhance memory performance and partially reverse the hypometabolism induced by chemotherapy. Although a feasibility study of donepezil in breast cancer survivors showed improvement in objective neurocognitive function, more research is necessary (20).

Physical Activity & Exercise

There is a plethora of research demonstrating the benefits of exercise for improved cognitive function. Animal and human studies support the use of exercise for chemotherapy-related neurocognitive function. Studies with cancer patients have documented neurocognitive improvements of exercise, including Qigong, Yoga, Tai Chi, physical fitness, and resistance training.

Cognitive Behavioral Therapy (CBT)

Neurocognitive changes frequently occur with anxiety, depression, fatigue, and sleep disturbances. CBT addresses the psychological response to neurocognitive change rather than the cause of neurologic injury. Memory and adaptation training (MAAT) is a form of CBT developed for patients with cancer. MAAT aims to build adaptive skills and reduce the disparity between cognitive demand and perceived ability to cope with cognitive demands. Improvements in cognitive performance have also been noted with compensatory and computer based cognitive training. Sustained performance improvements has been demonstrated months after CBT.

Evidence-Based Protocol

Based on a thorough review of the literature, we have developed an evidence-based strategy to address cancer treatment related cognitive impairment.

For more information, please email helpdesk@cancer-wellness.org or call 801-236-2294


  1. Harrison RA,, Wefel, J. Neurocognitive Function in Adult Cancer Patients. Neurol Clin. 2018 Aug;36(3):653-674.

  2. Wefel JS, Lenzi R, Theriault RL, Davis RN, Meyers CA. The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer, 2004;100:2292–9.

  3. Myers JS, Chemotherapy-related cognitive impairment. Clin J Oncol Nurs 2009;13:413–21.

  4. Tannock IF, Ahles TA, Ganz PA, Van Dam FS. Cognitive impairment associated with chemotherapy for cancer: report of a workshop. J Clin Oncol 2004;22:2233–9.

  5. Schagen SB, van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF. Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 1999;85:640–50.

  6. Brezden CB, Phillips KA, Abdolell M, Bunston T, Tannock IF. Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 2000;18:2695–701.

  7. Ahles TA, Saykin AJ, Furstenberg CT, Cole B, Mott LA, Skalla K, et al. Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol 2002;20:485–93.

  8. Tchen N, Juffs HG, Downie FP, Yi QL, Hu H, Chemerynsky I, et al. Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. J Clin Oncol 2003;21:4175–83.

  9. Joly F, Rigal O, Noal S, Giffard B. Cognitive dysfunction and cancer: which consequences in terms of disease management? Psychooncology 2011;20:1251–8.

  10. Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 2007;7:192–201.

  11. Krigel, S. Chemobrain—It's Real, It's Complex, and the Science Is Still Evolving. CURE. Feb, 17, 2015.

  12. Monje M, Dietrich J. Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis. Behav Brain Res 2012;227:376–9.

  13. Aluise CD, Miriyala S, Noel T, Sultana R, Jungsuwadee P, Taylor TJ, et al. 2-Mercaptoethane sulfonate prevents doxorubicin-induced plasma protein oxidation and TNF-alpha release: implications for the reactive oxygen species-mediated mechanisms of chemobrain. Free Radic Biol Med 2011;50:1630–8.

  14. Myers JS. The possible role of cytokines in chemotherapy-induced cognitive deficits. Adv Exp Med Biol 2010;678:119–23.

  15. Stemmer SM, Stears JC, Burton BS, Jones RB, Simon JH. White matter changes in patients with breast cancer treated with high-dose chemotherapy and autologous bone marrow support. AJNR Am J Neuroradiol 1994;15:1267–73.

  16. Deprez S, Amant F, Yigit R, Porke K, Verhoeven J, Van den Stock J, et al. Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. Hum Brain Mapp 2011;32:480–93.

  17. Silverman DH, Dy CJ, Castellon SA, Lai J, Pio BS, Abraham L, et al. Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. Breast Cancer Res Treat 2007;103:303–11.

  18. Denlinger, C., MD, Ligibel, A., Are, M. NCCN Clinical Practice Guidelines in Oncology: Survivorship: Cognitive Function, Version 1.201 2014 [Available On-line: 4http://www.jnccn.org/content/12/7/976.figures-only].

  19. Hara Y., Waters E.M., McEwen B.S., et al: Estrogen effects on cognitive and synaptic health over the lifecourse. Physiol Rev 2015; 95: pp. 785-807.

  20. Lim I., Joung H.Y., Yu A.R., et al: PET evidence of the effect of donepezil on cognitive performance in an animal model of chemobrain. Biomed Res Int 2016; 2016: pp. 6945415.

  21. Lawrence J.A., Griffin L., Balcueva E.P., et al: A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy. J Cancer Surviv 2016; 10: pp. 176-184.

  22. Zimmer P., Baumann F.T., Oberste M., et al: Effects of exercise interventions and physical activity behavior on cancer related cognitive impairments: a systematic review. Biomed Res Int 2016; 2016: pp. 1820954.

  23. Hotting K., and Roder B.: Beneficial effects of physical exercise on neuroplasticity and cognition. Neurosci Biobehav Rev 2013; 37: pp. 2243-2257.

  24. Mustian K.M., Sprod L.K., Janelsins M., et al: Exercise recommendations for cancer-related fatigue, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfunction: a review. Oncol Hematol Rev 2012; 8: pp. 81-88.

  25. Vardy J., Dhillon H.M., Pond G.R., et al: Cognitive function and fatigue after diagnosis of colorectal cancer. Ann Oncol 2014; 25: pp. 2404-2412.

  26. Shin S.Y., Katz P., and Julian L.: The relationship between perceived cognitive dysfunction and objective neuropsychological performance in persons with rheumatoid arthritis. Arthritis Care Res 2013; 65: pp. 481-486.

  27. Kinsinger S.W., Lattie E., and Mohr D.C.: Relationship between depression, fatigue, subjective cognitive impairment, and objective neuropsychological functioning in patients with multiple sclerosis. Neuropsychology 2010; 24: pp. 573-580

  28. Bender C.M., Pacella M.L., Sereika S.M., et al: What do perceived cognitive problems reflect? J Support Oncol 2008; 6: pp. 238-242.

  29. Kucherer S., and Ferguson R.J.: Cognitive behavioral therapy for cancer-related cognitive dysfunction. Curr Opin Support Palliat Care 2017; 11: pp. 46-51.

  30. Kucherer S., and Ferguson R.J.: Cognitive behavioral therapy for cancer-related cognitive dysfunction. Curr Opin Support Palliat Care 2017; 11: pp. 46-51.

  31. Ferguson R.J., Sigmon S.T., Pritchard A.J., et al: A randomized trial of videoconference-delivered cognitive behavioral therapy for survivors of breast cancer with self-reported cognitive dysfunction. Cancer 2016; 122: pp. 1782-1791.

  32. Ferguson R.J., McDonald B.C., Rocque M.A., et al: Development of CBT for chemotherapy-related cognitive change: results of a waitlist control trial. Psychooncology 2012; 21: pp. 176-186.

  33. Ferguson R.J., Ahles T.A., Saykin A.J., et al: Cognitive-behavioral management of chemotherapy-related cognitive change. Psychooncology 2007; 16: pp. 772-777.

  34. Park J.-H., Jung Y.S., Kim K.S., et al: Effects of compensatory cognitive training intervention for breast cancer patients undergoing chemotherapy: a pilot study. Support Care Cancer 2017; 25: pp. 1887-1896.

  35. Bail J., and Meneses K.: Computer-based cognitive training for chemotherapy-related cognitive impairment in breast cancer survivors. Clin J Oncol Nurs 2016; 20: pp. 504-509.

  36. Damholdt M.F., Mehlsen M., O'Toole M.S., et al: Web-based cognitive training for breast cancer survivors with cognitive complaints-a randomized controlled trial. Psychooncology 2016; 25: pp. 1293-1300.

  37. Von Ah D., Carpenter J.S., Saykin A., et al: Advanced cognitive training for breast cancer survivors: a randomized controlled trial. Breast Cancer Res Treat 2012; 135: pp. 799-809.