Skip to main content

Advertisement

SpringerLink
Log in

Cognitive impairment in gynecologic cancers: a systematic review of current approaches to diagnosis and treatment

  • Review Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

To review the etiology and assessment of chemotherapy-related cognitive impairment (CRCI). To explore current treatment and prevention strategies for CRCI and propose future research goals in the field of gynecologic oncology.

Methods

Computerized searches in PubMed of cognitive impairment in cancer between 2000 and 2012 were conducted. The inclusion criteria were randomized control trials evaluating treatment of CRCI and search terms 'cognitive function, cognitive impairment, cognitive decline, chemobrain, chemofog, and cancer'.

Results

To date, numerous modalities have been utilized for assessing CRCI in patients undergoing therapy. It has been proposed to move towards web-based assessment modalities as a possible standard. Few studies have aimed to elucidate possible treatment and prevention options for CRCI; even less in the field of gynecologic oncology. Only seven of these studies were subjected to randomized control trials. Only one of these studies looked at treatment in patients with gynecologic cancers.

Conclusions

The etiology of CRCI is multi-factorial. Following from this, there is no consensus on the best way to assess CRCI although objective measures are more reliable. One must extrapolate data from the non-gynecologic cancer literature, even venturing to non-cancer literature, to explore the treatment and prevention of CRCI. The methods found in these areas of research have not yet been applied to CRCI in gynecologic oncology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Vardy J, Wefel JS, Ahles T, Tannock IF, Schagen SB (2008) Cancer and cancer-therapy related cognitive dysfunction: an international perspective from the Venice Cognitive Workshop. Ann Oncol 19(4):623–629

    Article  CAS  PubMed  Google Scholar 

  2. 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):223–232

    Article  PubMed  Google Scholar 

  3. cancer.org. Chemo brain. http://www.cancer.org/Treatment/TreatmentsandSideEffects/PhysicalSideEffects/ChemotherapyEffects/chemo-brain. Accessed October, 2012

  4. Ahles TA, Saykin AJ (2007) Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 7(3):192–201

    Article  CAS  PubMed  Google Scholar 

  5. Kurita GP, Sjogren P, Ekholm O et al (2011) Prevalence and predictors of cognitive dysfunction in opioid-treated patients with cancer: a multinational study. J Clin Oncol 29(10):1297–1303

    Article  PubMed  Google Scholar 

  6. Stavraka C, Ford A, Ghaem-Maghami S et al (2012) A study of symptoms described by ovarian cancer survivors. Gynecol Oncol 125(1):59–64

    Article  PubMed  Google Scholar 

  7. Reid-Arndt SA (2009) Breast cancer and "chemobrain": the consequences of cognitive difficulties following chemotherapy and the potential for recovery. Mo Med 106(2):127–131

    PubMed  Google Scholar 

  8. Burton CL, Strauss E, Hultsch DF, Hunter MA (2006) Cognitive functioning and everyday problem solving in older adults. Clin Neuropsychol 20(3):432–452

    Article  PubMed  Google Scholar 

  9. Reiriz AB, Reolon GK, Preissler T, et al (2006) Cancer chemotherapy and cognitive function in rodent models: memory impairment induced by cyclophosphamide in mice. Clin Cancer Res;12(16):5000; author reply 5000–1

    Google Scholar 

  10. Dietrich J, Han R, Yang Y, Mayer-Proschel M, Noble M (2006) CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol 5(7):22

    Article  PubMed  Google Scholar 

  11. Han R, Yang YM, Dietrich J, Luebke A, Mayer-Proschel M, Noble M (2008) Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system. J Biol 7(4):12

    Article  PubMed  Google Scholar 

  12. Briones TL, Woods J (2011) Chemotherapy-induced cognitive impairment is associated with decreases in cell proliferation and histone modifications. BMC Neurosci 12:124

    Article  CAS  PubMed  Google Scholar 

  13. Gangloff A, Hsueh WA, Kesner AL et al (2005) Estimation of paclitaxel biodistribution and uptake in human-derived xenografts in vivo with (18)F-fluoropaclitaxel. J Nucl Med 46(11):1866–1871

    CAS  PubMed  Google Scholar 

  14. Mayerhofer K, Bodner K, Saletu B et al (2001) Paclitaxel–carboplatin chemotherapy does not cause encephalopathy in patients with ovarian cancer: a prospective EEG mapping study in 28 patients. Anticancer Res 21(1B):803–808

    CAS  PubMed  Google Scholar 

  15. Kreukels BP, Schagen SB, Ridderinkhof KR et al (2006) Effects of high-dose and conventional-dose adjuvant chemotherapy on long-term cognitive sequelae in patients with breast cancer: An electrophysiologic study. Clin Breast Cancer 7(1):67–78

    Article  CAS  PubMed  Google Scholar 

  16. Cheung YT, Chui WK, Chan A (2012) Neuro-cognitive impairment in breast cancer patients: pharmacological considerations. Crit Rev Oncol Hematol 83(1):99–111

    Article  PubMed  Google Scholar 

  17. Schagen SB, Hamburger HL, Muller MJ, Boogerd W, van Dam FS (2001) Neurophysiological evaluation of late effects of adjuvant high-dose chemotherapy on cognitive function. J Neurooncol 51(2):159–165

    Article  CAS  PubMed  Google Scholar 

  18. Madhyastha S, Somayaji SN, Rao MS, Nalini K, Bairy KL (2002) Hippocampal brain amines in methotrexate-induced learning and memory deficit. Can J Physiol Pharmacol 80(11):1076–1084

    Article  CAS  PubMed  Google Scholar 

  19. Walker CH, Drew BA, Antoon JW, Kalueff AV, Beckman BS (2012) Neurocognitive effects of chemotherapy and endocrine therapies in the treatment of breast cancer: recent perspectives. Cancer Invest 30(2):135–148

    Article  CAS  PubMed  Google Scholar 

  20. Aluise CD, Sultana R, Tangpong J et al (2010) Chemo brain (chemo fog) as a potential side effect of doxorubicin administration: role of cytokine-induced, oxidative/nitrosative stress in cognitive dysfunction. Adv Exp Med Biol 678:147–156

    CAS  PubMed  Google Scholar 

  21. Tsavaris N, Kosmas C, Vadiaka M, Kanelopoulos P, Boulamatsis D (2002) Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes. Br J Cancer 87(1):21–27

    Article  CAS  PubMed  Google Scholar 

  22. Pusztai L, Mendoza TR, Reuben JM et al (2004) Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine 25(3):94–102

    Article  CAS  PubMed  Google Scholar 

  23. Penson RT, Kronish K, Duan Z et al (2000) Cytokines IL-1beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFalpha in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel. Int J Gynecol Cancer 10(1):33–41

    Article  PubMed  Google Scholar 

  24. Lutgendorf SK, Weinrib AZ, Penedo F et al (2008) Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. J Clin Oncol 26(29):4820–4827

    Article  CAS  PubMed  Google Scholar 

  25. Szelenyi J (2001) Cytokines and the central nervous system. Brain Res Bull 54(4):329–338

    Article  CAS  PubMed  Google Scholar 

  26. Tangpong J, Sompol P, Vore M et al (2008) Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells. Neuroscience 151(2):622–629

    Article  CAS  PubMed  Google Scholar 

  27. Tangpong J, Cole MP, Sultana R et al (2006) Adriamycin-induced, TNF-alpha mediated central nervous system toxicity. Neurobiol Dis 23(1):127–139

    Article  CAS  PubMed  Google Scholar 

  28. Joshi G, Sultana R, Tangpong J et al (2005) Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain. Free Radic Res 39(11):1147–1154

    Article  CAS  PubMed  Google Scholar 

  29. Konat GW, Kraszpulski M, James I, Zhang HT, Abraham J (2008) Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats. Metab Brain Dis 23(3):325–333

    Article  CAS  PubMed  Google Scholar 

  30. Seigers R, Timmermans J, van der Horn HJ et al (2010) Methotrexate reduces hippocampal blood vessel density and activates microglia in rats but does not elevate central cytokine release. Behav Brain Res 207(2):265–272

    Article  CAS  PubMed  Google Scholar 

  31. Correa DD, Zhou Q, Thaler HT, Maziarz M, Hurley K, Hensley ML (2010) Cognitive functions in long-term survivors of ovarian cancer. Gynecol Oncol 119(2):366–369

    Article  PubMed  Google Scholar 

  32. Meyers CA (2000) Neurocognitive dysfunction in cancer patients. Oncology (Williston Park). ;14(1):75–9; discussion 79, 81–2, 85

  33. Meyers CA, Wefel JS (2003) The use of the mini-mental state examination to assess cognitive functioning in cancer trials: no ifs, ands, buts, or sensitivity. J Clin Oncol 21(19):3557–3558

    Article  PubMed  Google Scholar 

  34. Suri D, Vaidya VA (2012) Glucocorticoid regulation of brain-derived neurotrophic factor: relevance to hippocampal structural and functional plasticity. Neuroscience

  35. Aleman A, Torres-Aleman I (2009) Circulating insulin-like growth factor I and cognitive function: neuromodulation throughout the lifespan. Prog Neurobiol 89(3):256–265

    Article  CAS  PubMed  Google Scholar 

  36. Parker WH, Jacoby V, Shoupe D, Rocca W (2009) Effect of bilateral oophorectomy on women's long-term health. Womens Health (Lond Engl) 5(5):565–576

    Article  PubMed  Google Scholar 

  37. Vodermaier A (2009) Breast cancer treatment and cognitive function: the current state of evidence, underlying mechanisms and potential treatments. Womens Health (Lond Engl) 5(5):503–516

    Article  PubMed  Google Scholar 

  38. Loibl S, Lintermans A, Dieudonne AS, Neven P (2011) Management of menopausal symptoms in breast cancer patients. Maturitas 68(2):148–154

    Article  CAS  PubMed  Google Scholar 

  39. Dutta V (2011) Chemotherapy, neurotoxicity, and cognitive changes in breast cancer. J Cancer Res Ther 7(3):264–269

    Article  PubMed  Google Scholar 

  40. Hess LM, Chambers SK, Hatch K et al (2010) Pilot study of the prospective identification of changes in cognitive function during chemotherapy treatment for advanced ovarian cancer. J Support Oncol 8(6):252–258

    Article  PubMed  Google Scholar 

  41. Hermelink K, Kuchenhoff H, Untch M et al (2010) Two different sides of 'chemobrain': determinants and nondeterminants of self-perceived cognitive dysfunction in a prospective, randomized, multicenter study. Psychooncology 19(12):1321–1328

    Article  PubMed  Google Scholar 

  42. Hensley ML, Correa DD, Thaler H et al (2006) Phase I/II study of weekly paclitaxel plus carboplatin and gemcitabine as first-line treatment of advanced-stage ovarian cancer: pathologic complete response and longitudinal assessment of impact on cognitive functioning. Gynecol Oncol 102(2):270–277

    Article  CAS  PubMed  Google Scholar 

  43. Deprez S, Amant F, Smeets A et al (2012) Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol 30(3):274–281

    Article  PubMed  Google Scholar 

  44. Silverman DH, Dy CJ, Castellon SA et al (2007) Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. Breast Cancer Res Treat 103(3):303–311

    Article  CAS  PubMed  Google Scholar 

  45. Lower EE, Fleishman S, Cooper A et al (2009) Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. J Pain Symptom Manage 38(5):650–662

    Article  CAS  PubMed  Google Scholar 

  46. Mar Fan HG, Clemons M, Xu W et al (2008) A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer. Support Care Cancer 16(6):577–583

    Article  PubMed  Google Scholar 

  47. Kohli S, Fisher SG, Tra Y et al (2009) The effect of modafinil on cognitive function in breast cancer survivors. Cancer 115(12):2605–2616

    Article  CAS  PubMed  Google Scholar 

  48. Lundorff LE, Jonsson BH, Sjogren P (2009) Modafinil for attentional and psychomotor dysfunction in advanced cancer: a double-blind, randomised, cross-over trial. Palliat Med 23(8):731–738

    Article  CAS  PubMed  Google Scholar 

  49. O'Shaughnessy JA (2002) Effects of epoetin alfa on cognitive function, mood, asthenia, and quality of life in women with breast cancer undergoing adjuvant chemotherapy. Clin Breast Cancer 3(Suppl 3):S116–S120

    Article  PubMed  Google Scholar 

  50. Fan HG, Park A, Xu W et al (2009) The influence of erythropoietin on cognitive function in women following chemotherapy for breast cancer. Psychooncology 18(2):156–161

    Article  PubMed  Google Scholar 

  51. Jatoi A, Kahanic SP, Frytak S et al (2005) Donepezil and vitamin E for preventing cognitive dysfunction in small cell lung cancer patients: preliminary results and suggestions for future study designs. Support Care Cancer 13(1):66–69

    Article  PubMed  Google Scholar 

  52. Chan KK, Yao TJ, Jones B et al (2011) The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring. Ann Oncol 22(10):2241–2249

    Article  CAS  PubMed  Google Scholar 

  53. Attia A, Rapp SR, Case LD et al (2012) Phase II study of Ginkgo biloba in irradiated brain tumor patients: effect on cognitive function, quality of life, and mood. J Neurooncol 109(2):357–363

    Article  PubMed  Google Scholar 

  54. Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology (Berl) 210(4):453–469

    Article  CAS  PubMed  Google Scholar 

  55. Raffa RB (2011) Cancer 'survivor-care': I. The alpha7 nAChR as potential target for chemotherapy-related cognitive impairment. J Clin Pharm Ther 36(4):437–445

    Article  CAS  PubMed  Google Scholar 

  56. Speca M, Carlson LE, Goodey E, Angen M (2000) A randomized, wait-list controlled clinical trial: the effect of a mindfulness meditation-based stress reduction program on mood and symptoms of stress in cancer outpatients. Psychosom Med 62(5):613–622

    CAS  PubMed  Google Scholar 

  57. Biegler KA, Chaoul MA, Cohen L (2009) Cancer, cognitive impairment, and meditation. Acta Oncol 48(1):18–26

    Article  PubMed  Google Scholar 

  58. Oh B, Butow PN, Mullan BA et al (2012) Effect of medical qigong on cognitive function, quality of life, and a biomarker of inflammation in cancer patients: a randomized controlled trial. Support Care Cancer 20(6):1235–1242

    Article  PubMed  Google Scholar 

  59. Cohen K (1999) The way of qigong. 1st trade paperback ed. New York: Ballantine Books; 427

  60. Galantino ML, Greene L, Daniels L, Dooley B, Muscatello L, O'Donnell L (2012) Longitudinal impact of yoga on chemotherapy-related cognitive impairment and quality of life in women with early stage breast cancer: a case series. Explore (NY) 8(2):127–135

    Article  PubMed  Google Scholar 

  61. Fardell JE, Vardy J, Shah JD, Johnston IN (2012) Cognitive impairments caused by oxaliplatin and 5-fluorouracil chemotherapy are ameliorated by physical activity. Psychopharmacology (Berl) 220(1):183–193

    Article  CAS  PubMed  Google Scholar 

  62. Ferguson RJ, McDonald BC, Rocque MA et al (2012) Development of CBT for chemotherapy-related cognitive change: Results of a waitlist control trial. Psychooncology 21(2):176–186

    Article  PubMed  Google Scholar 

  63. Joly F, Rigal O, Noal S, Giffard B (2011) Cognitive dysfunction and cancer: which consequences in terms of disease management? Psychooncology 20(12):1251–1258

    Article  PubMed  Google Scholar 

  64. Mori T, Rezai-Zadeh K, Koyama N et al (2012) Tannic acid is a natural beta-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice. J Biol Chem 287(9):6912–6927

    Article  CAS  PubMed  Google Scholar 

  65. Sattler C, Toro P, Schonknecht P, Schroder J (2012) Cognitive activity, education and socioeconomic status as preventive factors for mild cognitive impairment and Alzheimer's disease. Psychiatry Res 196(1):90–95

    Article  PubMed  Google Scholar 

  66. Fardell JE, Vardy J, Johnston IN, Winocur G (2011) Chemotherapy and cognitive impairment: treatment options. Clin Pharmacol Ther 90(3):366–376

    Article  CAS  PubMed  Google Scholar 

  67. Grimmett C, Bridgewater J, Steptoe A, Wardle J (2011) Lifestyle and quality of life in colorectal cancer survivors. Qual Life Res 20(8):1237–1245

    Article  PubMed  Google Scholar 

  68. Scapagnini G, Vasto S, Abraham NG, Caruso C, Zella D, Fabio G (2011) Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. Mol Neurobiol 44(2):192–201

    Article  CAS  PubMed  Google Scholar 

  69. Hajjar I, Hart M, Chen YL et al (2012) Effect of antihypertensive therapy on cognitive function in early executive cognitive impairment: a double-blind randomized clinical trial. Arch Intern Med 172(5):442–444

    Article  PubMed  Google Scholar 

  70. Brinton LA, Sakoda LC, Frederiksen K et al (2007) Relationships of uterine and ovarian tumors to pre-existing chronic conditions. Gynecol Oncol 107(3):487–494

    Article  PubMed  Google Scholar 

  71. Wefel JS, Vardy J, Ahles T, Schagen SB (2011) International cognition and cancer task force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol 12(7):703–708

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

There are no financial conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. St. Joseph’s Hospital and Medical Center, Division of Gynecologic Oncology, 500 W. Thomas Road, Suite 600, Phoenix, AZ, 85013, USA

    Christine D. Craig, Bradley J. Monk, John H. Farley & Dana M. Chase

Authors
  1. Christine D. Craig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bradley J. Monk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John H. Farley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dana M. Chase
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dana M. Chase.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Craig, C.D., Monk, B.J., Farley, J.H. et al. Cognitive impairment in gynecologic cancers: a systematic review of current approaches to diagnosis and treatment. Support Care Cancer 22, 279–287 (2014). https://doi.org/10.1007/s00520-013-2029-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-013-2029-7

Keywords

Search

Navigation