Current Neurology and Neuroscience Reports

, Volume 12, Issue 3, pp 267–275 | Cite as

Chemotherapy-Related Cognitive Dysfunction

Neuro-Oncology (LE Abrey, Section Editor)

Abstract

Many cancer patients develop treatment-related cognitive dysfunction that affects their quality of life and can result in diminished functional independence. There is an emerging body of transdisciplinary research demonstrating that chemotherapeutic agents can produce neurobiological changes within the brain, which are associated with a constellation of cognitive changes that can result in decreased quality of life and functional independence. The increased incidence of cancer, coupled with longer survival times, has resulted in larger numbers of cancer survivors who are struggling with this neurotoxicity. This review summarizes the neuropsychological findings in patients with breast and brain cancer who receive systemic chemotherapy as well as the recent animal and imaging research elucidating the mechanisms by which these therapies impact brain structure, function, and consequent behavior.

Keywords

Cognition Chemotherapy Neurotoxicity 

Notes

Disclosure

Conflicts of interest: J.S. Wefel: has been a consultant for Roche, Eli Lilly, Genentech, Exelixis, and Geron; and has received grant support from AstraZeneca; S.B. Schagen: none.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Perry A, Schmidt RE. Cancer therapy-associated CNS neuropathology: an update and review of the literature. Acta Neuropathologica. 2006;111:197–212.PubMedCrossRefGoogle Scholar
  2. 2.
    Videnovic A, Semenow I, Chua-Adajar R, et al. Capecitabine-induced multifocal leukoencephalopathy: a report of five cases. Neurology. 2005;65:1792–4.PubMedCrossRefGoogle Scholar
  3. 3.
    • Dietrich J, Monje M, Wefel J, et al. Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist. 2008;13:1285–95. This review summarizes the clinical spectrum of chemotherapy- and radiation therapy–associated neurotoxicity with special emphasis on cognitive dysfunction.PubMedCrossRefGoogle Scholar
  4. 4.
    Wefel JS, Kayl AE, Meyers CA. Neuropsychological dysfunction associated with cancer and cancer therapies: a conceptual review of an emerging target. Br J Cancer. 2004;90:1691–6.PubMedGoogle Scholar
  5. 5.
    Shah RR. Mechanistic basis of adverse drug reactions: the perils of inappropriate dose schedules. Expert Opinion Drug Safety. 2005;4:103–28.CrossRefGoogle Scholar
  6. 6.
    Sul JK, DeAngelis LM. Neurologic complications of cancer chemotherapy. Sem Oncol. 2006;33:324–32.CrossRefGoogle Scholar
  7. 7.
    Sheline GE. Radiation therapy of brain tumors. Cancer. 1977;39:873–81.PubMedCrossRefGoogle Scholar
  8. 8.
    Jansen C, Miakowski C, Dodd M, et al. Potential mechanisms for chemotherapy-induced impairments in cognitive function. Oncol Nursing Forum. 2005;32:1151–63.CrossRefGoogle Scholar
  9. 9.
    Keime-Guibert F, Napolitano M, Delattre JY. Neurological complications of radiotherapy and chemotherapy. J Neurol. 1998;245:695–708.PubMedCrossRefGoogle Scholar
  10. 10.
    Delattre JY, Posner JB. Neurological complications of chemotherapy and radiation therapy. In: Aminoff MJ, editor. Neurology and general medicine. Secondth ed. New York: Churchill Livingstone; 1995. p. 421–45.Google Scholar
  11. 11.
    Wieneke MH, Dienst ER. Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer. Psycho-Oncology. 1995;4:61–6.CrossRefGoogle Scholar
  12. 12.
    van Dam FS, Schagen SB, Muller MJ, et al. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. J Natl Canc Inst. 1998;90(3):210–8.CrossRefGoogle Scholar
  13. 13.
    Schagen SB, van Dam FS, Muller MJ, et al. Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer. 1999;85(3):640–50.PubMedCrossRefGoogle Scholar
  14. 14.
    Brezden CB, Phillips KA, Abdolell M, et al. Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol. 2000;18(14):2695–701.PubMedGoogle Scholar
  15. 15.
    Ahles TA, Saykin AJ, Furstenberg CT, Cole B, et al. Neuropsychologic impact of standard dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol. 2002;20(2):485–93.PubMedCrossRefGoogle Scholar
  16. 16.
    Schagen SB, Muller MJ, Boogerd W, et al. Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients. Ann Oncol. 2002;13(9):1387–97.PubMedCrossRefGoogle Scholar
  17. 17.
    Tchen N, Juffs HG, Downie FP, et al. Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. J Clin Oncol. 2003;21(22):4175–83.PubMedCrossRefGoogle Scholar
  18. 18.
    Castellon SA, Ganz PA, Bower JE, et al. Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol. 2004;26(7):955–69.PubMedCrossRefGoogle Scholar
  19. 19.
    Wefel JS, Lenzi R, Theriault R, et al. Chemobrain' in breast carcinoma?: a prologue. Cancer. 2004;101(3):466–75.PubMedCrossRefGoogle Scholar
  20. 20.
    Wefel JS, Lenzi R, Theriault RL, et al. The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer. 2004;100(11):2292–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Cimprich B, So H, Ronis DL, Trask C. Pre-treatment factors related to cognitive functioning in women newly diagnosed with breast cancer. Psychooncology. 2005;14(1):70–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Donovan KA, Small BJ, Andrykowski MA, et al. Cognitive functioning after adjuvant chemotherapy and/or radiotherapy for early-stage breast carcinoma. Cancer. 2005;104(11):2499–507.PubMedCrossRefGoogle Scholar
  23. 23.
    Mar Fan HG, Houede-Tchen N, Yi QL, et al. Fatigue, menopausal symptoms, and cognitive function in women after adjuvant chemotherapy for breast cancer: 1- and 2-year follow-up of a prospective controlled study. J Clin Oncol. 2005;23(31):8025–32.CrossRefGoogle Scholar
  24. 24.
    Shilling V, Jenkins V, Morris R. The effects of adjuvant chemotherapy on cognition in women with breast cancer-preliminary results of an observational longitudinal study. Breast. 2005;14(2):142–50.PubMedCrossRefGoogle Scholar
  25. 25.
    Yoshikawa E, Matsuoka Y, Inagaki M, et al. No adverse effects of adjuvant chemotherapy on hippocampal volume in Japanese breast cancer survivors. Breast Canc Res Treat. 2005;92(1):81–4.CrossRefGoogle Scholar
  26. 26.
    Bender CM, Sereika SM, Berga SL, et al. Cognitive impairment associated with adjuvant therapy in breast cancer. Psychooncology. 2006;15(5):422–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Hurria A, Rosen C, Hudis C, et al. Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study. J Am Geriatr Soc. 2006;54(6):925–31.PubMedCrossRefGoogle Scholar
  28. 28.
    Inagaki M, Yoshikawa E, Matsuoka Y, et al. Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer. 2007;109(1):146–56.PubMedCrossRefGoogle Scholar
  29. 29.
    Jenkins V, Shilling V, Deutsch G, et al. A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer. 2006;94(6):828–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Schagen SB, Muller MJ, Boogerd W, et al. Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. J Natl Canc Inst. 2006;98(23):1742–5.CrossRefGoogle Scholar
  31. 31.
    Scherwath A, Mehnert A, Schleimer B, et al. Neuropsychological function in high-risk breast cancer survivors after stem-cell supported high-dose therapy versus standard-dose chemotherapy: evaluation of long-term treatment effects. Ann Oncol. 2006;17(3):415–23.PubMedCrossRefGoogle Scholar
  32. 32.
    Ahles TA, Saykin AJ, McDonald BC, et al. Cognitive function in breast cancer patients prior to adjuvant treatment. Breast Canc Res Treat. 2008;110(1):143–52.CrossRefGoogle Scholar
  33. 33.
    Hermelink K, Untch M, Lux MP, et al. Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study. Cancer. 2007;109(9):1905–13.PubMedCrossRefGoogle Scholar
  34. 34.
    • Abraham J, Haut MW, Moran MT, et al. Adjuvant chemotherapy for breast cancer: effects on cerebral white matter seen in diffusion tensor imaging. Clin Breast Cancer. 2008;8(1):88–91. This article is among the first to describe chemotherapy-associated changes in cerebral white matter related to cognitive deficits experienced by breast cancer patients.PubMedCrossRefGoogle Scholar
  35. 35.
    Minisini AM, De Faccio S, Ermacora P, et al. Cognitive functions and elderly cancer patients receiving anticancer treatment: a prospective study. Crit Rev Oncol Hematol. 2008;67(1):71–9. Epub 2008 Apr 3.PubMedCrossRefGoogle Scholar
  36. 36.
    Jansen CE, Dodd MJ, Miaskowski CA, et al. A longitudinal study of changes in cognitive function in breast cancer patients undergoing chemotherapy with doxorubicin and cyclophosphamide. Psycho-Oncology. 2008;17(12):1189–95.PubMedCrossRefGoogle Scholar
  37. 37.
    Stewart A, Collins B, Mackenzie J, et al. The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study. Psycho-Oncology. 2008;17(2):122–30.PubMedCrossRefGoogle Scholar
  38. 38.
    Kreukels BP, van Dam FS, Ridderinkhof KR, et al. Persistent neurocognitive problems after adjuvant chemotherapy for breast cancer. Clin Breast Cancer. 2008;8(1):80–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Weis J, Poppelreuter M, et al. Cognitive deficits as long-term side-effects of adjuvant therapy in breast cancer patients: 'subjective' complaints and 'objective' neuropsychological test results. Psycho-Oncology. 2009;18(7):775–82.PubMedCrossRefGoogle Scholar
  40. 40.
    Collins B, Mackenzie J, Stewart A, et al. Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment. Psycho-Oncology. 2009;18(2):134–43.PubMedCrossRefGoogle Scholar
  41. 41.
    Schilder CM, Eggens PC, Seynaeve C, et al. Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study. Acta Oncol. 2009;48(1):76–85.PubMedCrossRefGoogle Scholar
  42. 42.
    Jim HS, Donovan KA, Small BJ, et al. Cognitive functioning in breast cancer survivors: a controlled comparison. Cancer. 2009;115(8):1776–83.PubMedCrossRefGoogle Scholar
  43. 43.
    Kesler SR, Bennett FC, Mahaffey ML, et al. Regional brain activation during verbal declarative memory in metastatic breast cancer. Clin Cancer Res. 2009;15(21):6665–73.PubMedCrossRefGoogle Scholar
  44. 44.
    Mehlsen M, Pedersen AD, Jensen AB, et al. No indications of cognitive side effects in a prospective study of breast cancer patients receiving adjuvant chemotherapy. Psycho-Oncology. 2009;18(3):248–57.PubMedCrossRefGoogle Scholar
  45. 45.
    Ouimet LA, Stewart A, Collins B, et al. Measuring neuropsychological change following breast cancer treatment: an analysis of statistical models. J Clin Exp Neuropsychol. 2009;31(1):73–89.PubMedCrossRefGoogle Scholar
  46. 46.
    Quesnel C, Savard J, Ivers H. Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Canc Res Treat. 2009;116(1):113–23.CrossRefGoogle Scholar
  47. 47.
    • Reid-Arndt SA, Yee A, Perry MC, et al. Cognitive and psychological factors associated with early posttreatment functional outcomes in breast cancer survivors. J Psychosoc Oncol. 2009;27(4):415–34. This manuscript provides important insights into the functional impact of chemotherapy-related cognitive dysfunction.PubMedCrossRefGoogle Scholar
  48. 48.
    Vearncombe KJ, Rolfe M, Wright M, et al. Predictors of cognitive decline after chemotherapy in breast cancer patients. J Int Neuropsychol Soc. 2009;15(6):951–62.PubMedCrossRefGoogle Scholar
  49. 49.
    Ahles TA, Saykin AJ, McDonald BC, et al. Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol. 2010;28(29):4434–40.PubMedCrossRefGoogle Scholar
  50. 50.
    Cimprich B, Reuter-Lorenz P, Nelson J, et al. Prechemotherapy alterations in brain function in women with breast cancer. J Clin Exp Neuropsychol. 2010;32(3):324–31. Epub 2009 Jul 29.PubMedCrossRefGoogle Scholar
  51. 51.
    de Ruiter MB, Reneman L, Boogerd W, et al. Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer. Hum Brain Mapp. 2011;32(8):1206–19.PubMedCrossRefGoogle Scholar
  52. 52.
    Debess J, Riis JO, Engebjerg MC, et al. Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study. Breast Canc Res Treat. 2010;121(1):91–100.CrossRefGoogle Scholar
  53. 53.
    Jansen CE, Cooper BA, Dodd MJ, et al. A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients. Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer. 2011;19(10):1647–56.CrossRefGoogle Scholar
  54. 54.
    Kvale EA, Clay OJ, Ross-Meadows LA, et al. Cognitive speed of processing and functional declines in older cancer survivors: an analysis of data from the ACTIVE trial. Eur J Cancer Care. 2010;19(1):110–7.CrossRefGoogle Scholar
  55. 55.
    Reid-Arndt SA, Hsieh C, Perry MC. Neuropsychological functioning and quality of life during the first year after completing chemotherapy for breast cancer. Psycho-Oncology. 2010;19(5):535–44.PubMedCrossRefGoogle Scholar
  56. 56.
    Tager FA, McKinley PS, Schnabel FR, et al. The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study. Breast Canc Res Treat. 2010;123(1):25–34.CrossRefGoogle Scholar
  57. 57.
    • Wefel JS, Saleeba AK, Buzdar AU, et al. Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer. 2010;116(14):3348–56. This prospective study shows that standard-dose chemotherapy is associated with decline in cognitive functioning during and shortly after chemotherapy, and indicates the occurrence of new delayed cognitive decline in a considerable proportion of patients.PubMedCrossRefGoogle Scholar
  58. 58.
    Yamada TH, Denburg NL, Beglinger LJ, et al. Neuropsychological outcomes of older breast cancer survivors: cognitive features ten or more years after chemotherapy. J Neuropsychiatry Clin Neurosci. 2010;22(1):48–54.PubMedCrossRefGoogle Scholar
  59. 59.
    Kesler SR, Kent JS, O'Hara R. Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol. 2011;68(11):1447–53.PubMedCrossRefGoogle Scholar
  60. 60.
    • Deprez S, Amant F, Yigit R, 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(3):480–93. This study demonstrates that DTI provides white matter integrity parameters that are sensitive to investigate neural changes related to cognitive problems in cancer patients following chemotherapy.PubMedCrossRefGoogle Scholar
  61. 61.
    Biglia N, Bounous VE, Malabaila A, et al. Objective and self-reported cognitive dysfunction in breast cancer women treated with chemotherapy: a prospective study. Eur J Cancer Care 2011, doi:  10.1111/j.1365-2354.2011.01320.x. [Epub ahead of print]
  62. 62.
    Koppelmans V, Breteler MMB, Boogerd W, et al. Neuropsychological performance in breast cancer survivors more than 20 years after adjuvant chemotherapy. Journal of Clinical Oncology 2012; in pressGoogle Scholar
  63. 63.
    Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer. 2007;7(3):192–201.PubMedCrossRefGoogle Scholar
  64. 64.
    Schilder CM, Seynaeve C, Beex LV, et al. Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial. J Clin Oncol. 2010;28(8):1294–300. Epub 2010 Feb 8.PubMedCrossRefGoogle Scholar
  65. 65.
    Reardon DA, Galanis E, DeGroot JF, et al. Clinical trial end points for high-grade glioma: the evolving landscape. Neuro-Oncology. 2011;13:353–61.PubMedCrossRefGoogle Scholar
  66. 66.
    Wefel JS, Cloughesy T, Zazzali JL, et al. Neurocognitive function in patients with recurrent glioblastoma treated with bevacizumab. Neuro Oncol. 2011;13:660–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the CNS. Int J Radiat Oncol Biol Phys. 2011;79:1487–95.PubMedCrossRefGoogle Scholar
  68. 68.
    Wefel JS, Armstrong TS, Wang M et al. Clinical utility of neurocognitive function as a prognostic factor for survival and measure of differential between-arm treatment effects on RTOG 0525. Presented at the 2011 Society for Neuro-Oncology Meeting in Collaboration with the AANS/CNS Section on Tumors. Orange County, CA; November 17-20, 2011.Google Scholar
  69. 69.
    Hilverda K, Bosma I, Heimans JJ, et al. Cognitive functioning in glioblastoma patients during radiotherapy and temozolomide treatment: initial findings. J Neurooncol. 2010;97:89–94.PubMedCrossRefGoogle Scholar
  70. 70.
    Radiation Therapy Oncology Group: RTOG 9402 Finds Chromosomal Abnormality be a Strong Indicator for Determining Treatment and Outcome for Patients with Oligodendroglioma Brain Tumors. Available at http://www.rtog.org/News/tabid/72/articleType/ArticleView/articleId/31/RTOG-9402-Finds-Chromosomal-Abnormality-be-a-Strong-Indicator-for-Determining-Treatment-and-Outcome-for-Patients-with-Oligodendroglioma-Brain-Tumors.aspx. Accessed February 2012.
  71. 71.
    Levin VA, Yung WKA, Bruner J, et al. Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of analplastic gliomas. Int J Radiat Oncol Biol Phys. 2002;53:58–66.PubMedCrossRefGoogle Scholar
  72. 72.
    Groves MD, Maor MH, Meyers C, et al. A phase II trial of high-dose bromodeoxyuridine with accelerated fractionation radiotherapy followed by procarbazine, lomustine, and vincristine for glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 1999;45:127–35.PubMedCrossRefGoogle Scholar
  73. 73.
    Correa DD, Maron L, Harder H, et al. Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines. Ann Oncol. 2007;18:1145–51.PubMedCrossRefGoogle Scholar
  74. 74.
    Correa DD, Rocco-Donovan M, DeAngelis LM, et al. Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy. J Neurooncol. 2009;91:315–21.PubMedCrossRefGoogle Scholar
  75. 75.
    Brown MS, Simon JH, Stemmer SM, et al. MR and proton spectroscopy of white matter disease induced by high-dose chemotherapy with bone marrow transplant in advanced breast carcinoma. AJNR Am J Neuroradiol. 1995;16(10):2013–20.PubMedGoogle Scholar
  76. 76.
    Choi SM, Lee SH, Yang YS, et al. 5-fluorouracil-induced leukoencephalopathy in patients with breast cancer. J Korean Med Sci. 2001;16(3):328–34.PubMedGoogle Scholar
  77. 77.
    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;25:3866–70.PubMedCrossRefGoogle Scholar
  78. 78.
    de Ruiter MB, Reneman L, Boogerd W, et al. Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging. Hum Brain Mapp 2011;In Press.Google Scholar
  79. 79.
    Koppelmans V, de Ruiter MB, van der Lijn F et al. Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy. Breast Cancer Res Treat 2011, Epub Dec 29.Google Scholar
  80. 80.
    Brown MS, Stemmer SM, Simon JH, et al. White matter disease induced by high-dose chemotherapy: longitudinal study with MR imaging and proton spectroscopy. AJNR Am J Neuroradiol. 1998;19(2):217–21.PubMedGoogle Scholar
  81. 81.
    • McDonald BC, Conroy SK, Ahles TA, et al. Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat. 2010;123(3):819–28. This study is the first study showing evidence of longitudinal changes in cognitive functioning and cerebral white matter integrity after chemotherapy as well as an association between both.PubMedCrossRefGoogle Scholar
  82. 82.
    Silverman DH, Dy CJ, Castellon SA, 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.PubMedCrossRefGoogle Scholar
  83. 83.
    Scherling C, Collins B, Mackenzie J, et al. Pre-chemotherapy differences in visuospatial working memory in breast cancer patients compared to controls: an FMRI study. Front Hum Neurosci 2011,5:122 Epub Nov 1.Google Scholar
  84. 84.
    •• Seigers R, Fardell JE. Neurobiological basis of chemotherapy-induced cognitive impairment: a review of rodent research. Neurosci Biobehav Rev. 2011;35:729–41. This manuscript comprehensively reviews the recent animal literature regarding the effects of different classes of cytotoxic agents on behavior and neurobiology.PubMedCrossRefGoogle Scholar
  85. 85.
    Monje M, Dietrich J. Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis. Behavioral Brain Research. 2011;227:376–9.CrossRefGoogle Scholar
  86. 86.
    Gong X, Schwartz PH, Linskey ME, et al. Neural stem/progenitors and glioma stem-like cells have differential sensitivity to chemotherapy. Neurology. 2011;76:1126–34.PubMedCrossRefGoogle Scholar
  87. 87.
    • Konat GW, Kraszpulski M, James I, et al. Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats. Metab Brain Dis. 2008;23:325–33. This study shows that N-acetyl cysteine ameliorated cognitive impairment due to cyclophosphamide and doxorubicin co-treatment, suggesting that oxidative stress may in part cause cognitive impairment associated with chemotherapy.PubMedCrossRefGoogle Scholar
  88. 88.
    Lyons L, Elbeltagy M, Bennett G, et al. Fluoxetine counteracts the cognitive and cellular effects of 5-fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery. PLoS ONE 2012, Epub January 2012.Google Scholar
  89. 89.
    Vijayanathan V, Gulinello M, Ali N, et al. Persistent cognitive deficits, induced by intrathecal methotrexate, are associated with elevated CSF concentrations of excitotoxic glutamate analogs and can be reversed by an NMDA antagonist. Behavioral Brain Research. 2011;225:491–7.CrossRefGoogle Scholar
  90. 90.
    Deeken JF, Loscher W. The blood-brain barrier and cancer: transporters, treatment and Trojan horses. Clin Cancer Res. 2007;13:1663–74.PubMedCrossRefGoogle Scholar
  91. 91.
    Lockman PR, Mittapali RK, Taskar KS, et al. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res. 2010;16:5664–78.PubMedCrossRefGoogle Scholar
  92. 92.
    • Wefel JS, Vardy J, Ahles T, et al. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12:703–8. This manuscript describes methodological challenges in this literature and recommends study designs, cognitive tests, and analytical methods to help harmonize clinical research in this area.PubMedCrossRefGoogle Scholar
  93. 93.
    van den Bent M, Wefel J, Schiff D, et al. Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas. Lancet Oncol. 2011;12:583–93.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Neuro-OncologyMD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Psychosocial Research and EpidemiologyNetherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands

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