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Supportive Care in Cancer

, Volume 22, Issue 8, pp 2251–2260 | Cite as

Neuropsychological care and rehabilitation of cancer patients with chemobrain: strategies for evaluation and intervention development

  • Pascal Jean-PierreEmail author
  • Douglas Johnson-Greene
  • Thomas G. Burish
Original Article

Abstract

Malignant tumors and their various treatments such as chemotherapy, radiotherapy and hormonal therapy can deleteriously affect a large number of cancer patients and survivors on multiple dimensions of psychosocial and neurocognitive functioning. Oncology researchers and clinicians are increasingly cognizant of the negative effects of cancer and its treatments on the brain and its mental processes and cognitive outcomes. Nevertheless, effective interventions to treat cancer and treatment-related neurocognitive dysfunction (CRND), also known as chemobrain, are still lacking. The paucity of data on effective treatments for CRND is due, at least partly, to difficulties understanding its etiology, and a lack of reliable methods for assessing its presence and severity. This paper provides an overview of the incidence, etiology, and magnitude of CRND, and discusses the plausible contributions of psychological, motor function, and linguistic and behavioral complications to CRND. Strategies for reliable neuropsychological screening and assessment, and development and testing of effective ways to mitigate CRND are also discussed.

Keywords

Cancer and treatment-related neurocognitive dysfunction Chemobrain Cancer and memory problems Cognitive functioning Neuropsychological tests Chemotherapy Cancer and cognition Cognitive disorders Neoplasms Malignant tumors Mental performance 

Notes

Acknowledgements

Dr. Pascal Jean-Pierre acknowledges the support of the Walther Cancer Foundation, the Indiana University Clinical and Translational Science Institute (IU-CTSI), and the Harper Cancer Research Institute. This study was made possible in part by the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award Grant Number TR000163 (A. Shekhar, PI).

Conflict of interest

The authors have no conflict of interest to declare. The authors have full control of all primary data and agree to allow the journal to review their data if requested.

References

  1. 1.
    Ahles TA, Saykin A, Furstenberg CT, Cole B, Mott LA, Skalla K et al (2002) Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol 20:485–493PubMedCrossRefGoogle Scholar
  2. 2.
    Brezden CB, Phillips KA, Abdolell M, Bunston T, Tannock IF (2000) Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 18:2695–701PubMedGoogle Scholar
  3. 3.
    Saykin AJ, Ahles TA, McDonald BC (2003) Mechanisms of chemotherapy induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives. Semin Clin Neuropsychiatry 8:201–216PubMedCrossRefGoogle Scholar
  4. 4.
    Schagen SB, van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF (1999) Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 85:640–650PubMedCrossRefGoogle Scholar
  5. 5.
    Scheibel RS, Valentine AD, O'Brien S, Meyers CA (2004) Cognitive dysfunction and depression during treatment with interferon-alpha and chemotherapy. J Neuropsychiatry Clin Neurosci 16(2):185–91PubMedCrossRefGoogle Scholar
  6. 6.
    Wefel JS, Lenzi R, Theriault R, Buzdar AU, Cruickshank S (2004) Meyers CA'.Chemobrain' in breast carcinoma?: a prologue. Cancer 101(3):466–75PubMedCrossRefGoogle Scholar
  7. 7.
    Correa DD, Ahles TA (2008) Neurocognitive changes in cancer survivors. Cancer J 14(6):396–400PubMedCrossRefGoogle Scholar
  8. 8.
    Tannock IF, Ahles TA, Ganz PA, van Dam FS (2004) Cognitive impairment associated with chemotherapy for cancer: report of a workshop. J Clin Oncol 22:2233–2239PubMedCrossRefGoogle Scholar
  9. 9.
    Boykoff N, Moieni M, Subramanian SK (2009) Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response. J Cancer Surviv 3(4):223–232PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Koppelmans V, Breteler M, Boogerd W, Seynaeve C, Gundy C, Schagen S (2012) Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol 30:1080–1086PubMedCrossRefGoogle Scholar
  11. 11.
    Jean-Pierre P, Winters PC, Ahles T, Antoni M, Armstrong FD, Penedo F, Lipshultz SE, Miller TL, Fiscella K (2012) Prevalence of memory problems in adult cancer survivors: a national cross-sectional study. J Oncol Pract 8(1):32–34CrossRefGoogle Scholar
  12. 12.
    Bradbury J (2006) Chemobrain: imaging shows changes in metabolism. Lancet Oncol 7(11):890PubMedCrossRefGoogle Scholar
  13. 13.
    Ahles TA, Saykin AJ (2007) Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 7(3):192–201PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Verstappen CCP, Heimans JJ, Hoekman K, Postma TJ (2003) Neurotoxic complications of chemotherapy in patients with cancer: clinical signs and optimal management. Drugs 63:1549–1563PubMedCrossRefGoogle Scholar
  15. 15.
    Dietrich J, Han R, Yang Y, Mayer M, Noble M (2006) CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol 5:22PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Rolig RL, McKinnon PJ (2000) Linking DNA damage and neurodegeneration. Trends Neurosci 23:417–424PubMedCrossRefGoogle Scholar
  17. 17.
    Kannarkat G, Lasher EE, Schiff D (2007 Dec) Neurologic complications of chemotherapy agents. Curr Opin Neurol 20(6):719–25Google Scholar
  18. 18.
    Ahles TA, Saykin AJ, McDonald BC, Li Y, Furstenberg CT, Hanscom BS, Mulrooney TJ, Schwartz GN, Kaufman PA (2010) Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol 28(29):4434–4440PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Joly F, Rigal O, Noal S, Giffard B (2011) Cognitive dysfunction and cancer: which consequences in terms of disease management? Psychooncology 20(12):1251–1258PubMedCrossRefGoogle Scholar
  20. 20.
    Saini A, Berruti A, Cracco C, Sguazzotti E, Porpiglia F, Russo L, Bertaglia V, Picci RL, Negro M, Tosco A, Campagna S, Scarpa RM, Dogliotti L, Furlan PM, Ostacoli L (2011) Psychological distress in men with prostate cancer receiving adjuvant androgen-deprivation therapy. Urol Oncol. Jul 29. [Epub ahead of print]Google Scholar
  21. 21.
    DiBlasio CJ, Hammett J, Malcolm JB, Judge BA, Womack JH, Kincade MC, Ogles ML, Mancini JG, Patterson AL, Wake RW, Derweesh IH (2008) Prevalence and predictive factors for the development of de novo psychiatric illness in patients receiving androgen deprivation therapy for prostate cancer. Can J Urol 15(5):4249–56PubMedGoogle Scholar
  22. 22.
    Kerestes R, Ladouceur CD, Meda S, Nathan PJ, Blumberg HP, Maloney K, Ruf B, Saricicek A, Pearlson GD, Bhagwagar Z, Phillips ML (2011) Abnormal prefrontal activity subserving attentional control of emotion in remitted depressed patients during a working memory task with emotional distracters. Psychol Med 7:1–12Google Scholar
  23. 23.
    Lisiecka DM, Carballedo A, Fagan AJ, Ferguson Y, Meaney J, Frodl T (2012) Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression. J Psychiatry Neurosci 37(6):110188Google Scholar
  24. 24.
    Kizilbash AH, Vanderploeg RD, Curtiss G (2002) The effects of depression and anxiety on memory performance. Arch Clin Neuropsychol 17(1):57–67PubMedCrossRefGoogle Scholar
  25. 25.
    Balash Y, Mordechovich M, Shabtai H, Giladi N, Gurevich T, Korczyn AD (2012)Subjective memory complaints in elders: depression, anxiety, or cognitive decline? Acta Neurol Scand Dec 6. doi:  10.1111/ane.12038. [Epub ahead of print]
  26. 26.
    Milne AM, Macqueen GM, Hall GB (2011) Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study. J Psychiatry Neurosci 36(4):110004. doi: 10.1503/jpn.110004. [Epub ahead of print]. PMID: 21745440Google Scholar
  27. 27.
    Sievers C, Sämann PG, Pfister H, Dimopoulou C, Czisch M, Roemmler J, Schopohl J, Stalla GK, Zihl J (2011) Cognitive function in acromegaly: description and brain volumetric correlates. Pituitary Jul 7. [Epub ahead of print]. PMID: 21735089Google Scholar
  28. 28.
    Bird CM, Burgess N (2008) The hippocampus and memory: insight from spatial processing. Nat Rev Neurosci 9:182–194. doi: 10.1038/nrn2335 PubMedCrossRefGoogle Scholar
  29. 29.
    Schiepers OJ, Wichers MC, Maes M (2005) Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 29(2):201–17, Epub 2005 Jan 25PubMedCrossRefGoogle Scholar
  30. 30.
    Maes M (1999) Major depression and activation of the inflammatory response system. Adv Exp Med Biol 461:25–46PubMedCrossRefGoogle Scholar
  31. 31.
    Cleeland CS, Bennett GJ, Dantzer R, Dougherty PM, Dunn AJ, Meyers CA, Miller AH, Payne R, Reuben JM, Wang XS, Lee BN (2003) Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 97:2919–25PubMedCrossRefGoogle Scholar
  32. 32.
    Raffa RB (2011) Cancer 'survivor-care': I. the α7 nAChR as potential target for chemotherapy-related cognitive impairment. J Clin Pharm Ther 36(4):437–45PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Marques AH, Silverman MN, Ester EM (2009) Glucocorticoid dysregulations and their clinical correlates. Ann NY Acad Sci 1179:1–18PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Alexopoulos GS, Morimoto SS. The inflammation hypothesis in geriatric depression (2011) Int J Geriatr Psychiatry Mar 2. doi:  10.1002/gps.2672. [Epub ahead of print]
  35. 35.
    Capuron L, Miller AH (2011) Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther 130(2):226–38, Epub 2011 Feb 17PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Conti CM, Fulcheri M (2010) Interrelationship between psychology and cytokines. J Biol Regul Homeost Agents 24(4):485–90PubMedGoogle Scholar
  37. 37.
    Monje ML, Mizumatsu S, Fike JR, Palmer TD (2002) Irradiation induces neural precursor-cell dysfunction. Nat Med 8(9):955–62, Epub 2002 Aug 5PubMedCrossRefGoogle Scholar
  38. 38.
    Jacobs BL, van Praag H, Gage FH (2000) Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 5(3):262–9, ReviewPubMedCrossRefGoogle Scholar
  39. 39.
    Otten ML, Mikell CB, Youngerman BE, Liston C, Sisti MB, Bruce JN, Small SA, McKhann GM II (2012) Motor deficits correlate with resting state motor network connectivity in patients with brain tumours. Brain 135(Pt 4):1017–26PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Miceli G, Capasso R, Monti A, Santini B, Talacchi A (2012) Language testing in brain tumor patients. J Neurooncol 108(2):247–52PubMedCrossRefGoogle Scholar
  41. 41.
    Dwivedi RC, St Rose S, Chisholm EJ, Bisase B, Amen F, Nutting CM, Clarke PM, Kerawala CJ, Rhys-Evans PH, Harrington KJ, Kazi R (2012) Evaluation of speech outcomes using English version of the Speech Handicap Index in a cohort of head and neck cancer patients. Oral Oncol 48(6):547–53PubMedCrossRefGoogle Scholar
  42. 42.
    Cramp F, Byron-Daniel J (2012) Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 11:CD006145. doi: 10.1002/14651858.CD006145.pub3. PMID: 23152233 [PubMed — in process]PubMedGoogle Scholar
  43. 43.
    de Raaf PJ, de Klerk C, van der Rijt CC (2012) Elucidating the behavior of physical fatigue and mental fatigue in cancer patients: a review of the literature. Psychooncology doi:  10.1002/pon.3225. [Epub ahead of print]
  44. 44.
    Bower JE (2012) Treating cancer-related fatigue: the search for interventions that target those most in need. J Clin Oncol 30(36):4449–50PubMedCrossRefGoogle Scholar
  45. 45.
    Donovan KA, McGinty HL, Jacobsen PB (2012)A systematic review of research using the diagnostic criteria for cancer-related fatigue. Psychooncology Apr 30. doi:  10.1002/pon.3085. [Epub ahead of print]. PMID: 22544488 [PubMed — as supplied by publisher]
  46. 46.
    Jean-Pierre P, Morrow GR, Roscoe JA, Heckler C, Mohile S, Janelsins M, Peppone L, Hemstad A, Esparaz BT, Hopkins JO (2010) A phase 3 randomized, placebo-controlled, double-blind, clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy: a University of Rochester Cancer Center Community Clinical Oncology Program Research base study. Cancer 116(14):3513–20PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Heaton SK, Heaton RK (1981) Testing the impaired patient. In: Filkowv SB, Boll TJ (eds) Handbook of clinical neuropsychology, vol Volume 1. Wiley, New York, pp pp. 425–544Google Scholar
  48. 48.
    Hibbard MR, Gordon WA (1992) The comprehensive psychological assessment of individuals with stroke. NeuroRehabilitation 2:9–20Google Scholar
  49. 49.
    Roth E, Davidoff G, Thomas P, Doljanac R, Dijkers M, Berent S, Morris J, Yarkony G (1989) A controlled study of neuropsychological deficits in acute spinal cord injury patients. Paraplegia 27:480–489PubMedCrossRefGoogle Scholar
  50. 50.
    Berninger V, Robinson R, Price T, Squires N (1988) Modified WAIS-R for patients with speech and/or hand dysfunction. Arch Phys Med Rehabil 69:250–255PubMedGoogle Scholar
  51. 51.
    Caplan BSJ (1995) The role of nonstandard neuropsychological assessment in rehabilitation: history, rationale, and examples. In: Scherer LCM (ed) Psychological assessment in medical rehabilitation. American Psychological Association, Washington, D.C, pp p. 359–391CrossRefGoogle Scholar
  52. 52.
    Stewart A, Bielajew C, Collins B, Parkinson M, Tomiak E (2000) A meta-analysis of the neuropsychological effects of adjuvant chemotherapy treatment in women treated for breast cancer. Clin Neuropsychol 20:76–89CrossRefGoogle Scholar
  53. 53.
    Weis J, Poppelreuter M, Bartsch HH (2009) Cognitive deficits as long-term side-effects of adjuvant therapy in breast cancer patients: 'subjective' complaints and 'objective' neuropsychological test results. Psycho-oncology 18:775–82PubMedCrossRefGoogle Scholar
  54. 54.
    Cicerone KD, Dahlberg C, Malec JF, Langenbahn DM, Felicetti C et al (2005) Evidenced-based cognitive rehabilitation: updated review of the literature from 1998 to 2002. Arch Phys Med Rehabil 11:19–39Google Scholar
  55. 55.
    Biegler KA, Chaoul MA, Cohen L (2009) Cancer, cognitive impairment, and meditation. Acta Oncol 48(1):18–26PubMedCrossRefGoogle Scholar
  56. 56.
    Ferguson RJ, Ahles TA, Saykin AJ, McDonald BC, Furstenberg CT, Cole BF, Mott LA (2007) Cognitive–behavioral management of chemotherapy-related cognitive change. Psychooncology 16(8):772–777PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Ratey JJ, Hagerman ES (2008) The revolutionary new science of exercise and the brain. Little Brown and Company, New YorkGoogle Scholar
  58. 58.
    Culos-Reed SN, Carlson LE, Daroux LM, Hately-Aldous S (2006) A pilot study of yoga for breast cancer survivors: physical and psychological benefits. Psychooncology 15(10):891–7PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Pascal Jean-Pierre
    • 1
    Email author
  • Douglas Johnson-Greene
    • 2
  • Thomas G. Burish
    • 3
  1. 1.Department of Psychology, Neurocognitive Translational Research Laboratory, Cancer Control and Survivorship ProgramUniversity of Notre DameNotre DameUSA
  2. 2.Department of Rehabilitation MedicineUniversity of Miami School of MedicineMiamiUSA
  3. 3.Department of PsychologyUniversity of Notre DameNotre DameUSA

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