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Journal of Cancer Survivorship

, Volume 13, Issue 2, pp 231–243 | Cite as

Cognitive functioning in thyroid cancer survivors: a systematic review and meta-analysis

  • Omar Saeed
  • Lori J. Bernstein
  • Rouhi Fazelzad
  • Mary Samuels
  • Lynn A. Burmeister
  • Lehana Thabane
  • Shereen Ezzat
  • David P. Goldstein
  • Jennifer Jones
  • Anna M. SawkaEmail author
Review

Abstract

Background

Some thyroid cancer (TC) survivors experience cognitive symptoms.

Purpose

The purpose of this study is to perform a systematic literature review and meta-analysis comparing cognitive performance in TC survivors to controls.

Methods

We performed a seven-database electronic search and hand-search. We performed duplicate independent reviews and data abstraction. Random effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), where a negative value implies worse performance in the TC group.

Results

We reviewed 1174 unique citations and 10 full-text papers. We included seven studies of 241 treated TC survivors and 273 controls. Cognitive function was statistically significantly worse in TC survivors in the following domains: Attention and Concentration (Digit Span Forwards) SMD − 0.37 (95% CI − 0.62, − 0.13, p = 0.003, four studies), Speed of Processing (Trail Making A) SMD − 0.36 (95% CI − 0.66, − 0.05, p = 0.022, four studies), and Language (Controlled Oral Word Association [COWAT]-Categories) SMD − 0.97 (95% − 1.31, − 0.64, p < 0.001, two studies). Executive Function results varied: COWAT-Letters SMD − 0.60 (95% CI − 0.94, − 0.27, p < 0.001, two studies), Digit Span Backwards SMD − 0.40 (95% CI − 0.64, − 0.15, p = 0.002, four studies), and Trail Making B test SMD − 0.20 (95% CI − 0.51, 0.10, p = 0.191, four studies). Statistical heterogeneity limited the COWAT-Categories and Digit Span Backwards meta-analyses.

Conclusions

Cognitive function was worse in TC survivors in multiple domains. Limitations included few studies, potential confounding, and lack of prospective data.

Implications for Cancer Survivors

TC survivors may experience impairments in cognitive function and should report cognitive concerns to healthcare practitioners.

Keywords

Neurocognitive function Cancer survivorship Thyroid cancer Systematic review Meta-analysis 

Notes

Acknowledgments

AMS was supported, in part, by a University of Toronto Department of Medicine Clinician Scientist Merit Award. The authors would like to thank Mrs. Coreen Marino, for assistance in retrieving the full-text papers for review. The authors would also like to thank Drs. Jan Jaracz and Moira A. Visovatti, for kindly responding to our queries about their studies.

Funding information

Library service expenses were funded, in part, from a University Health Network Thyroid Cancer Research Fund (private charitable donations to the UHN Foundation).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    La Vecchia C, Malvezzi M, Bosetti C, Garavello W, Bertuccio P, Levi F, et al. Thyroid cancer mortality and incidence: a global overview. Int J Cancer. 2015;136(9):2187–95.CrossRefGoogle Scholar
  2. 2.
    International Agency for Research on Cancer 2017 GLOBOCAN 2012: Estimated cancer incidence, mortality, and prevalence worldwide in 2012. Available at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx Accessed July 18, 2018.
  3. 3.
    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. for the American Thyroid Association 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1–133.CrossRefGoogle Scholar
  4. 4.
    Rosenthal K. When cancer muddles the mind. 2009 New York Times. Available at: https://well.blogs.nytimes.com/2009/11/17/when-cancer-muddles-the-mind/ Accessed July 18, 2018.
  5. 5.
    Joly F, Giffard B, Rigal O, De Ruiter MB, Small BJ, Dubois M, et al. Impact of cancer and its treatments on cognitive function: advances in research from the Paris International Cognition and Cancer Task Force Symposium and Update since 2012. J Pain Symptom Manag. 2015;50(6):830–41.CrossRefGoogle Scholar
  6. 6.
    Ahles TA, Root JC. Cognitive effects of cancer and cancer treatments. Annu Rev Clin Psychol. 2018;14:425–51.CrossRefGoogle Scholar
  7. 7.
    Bernstein LJ, McCreath GA, Komeylian Z, Rich JB. Cognitive impairment in breast cancer survivors treated with chemotherapy depends on control group type and cognitive domains assessed: a multilevel meta-analysis. Neurosci Biobehav Rev. 2017;83:417–28.CrossRefGoogle Scholar
  8. 8.
    Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158(4):280–6.CrossRefGoogle Scholar
  9. 9.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.CrossRefGoogle Scholar
  10. 10.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;73:177–88.CrossRefGoogle Scholar
  11. 11.
    Cochrane WG. The combination of estimates from different experiments. Biometrics. 1954;101:101–29.CrossRefGoogle Scholar
  12. 12.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;3277414:557–60.CrossRefGoogle Scholar
  13. 13.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;3157109:629–34.CrossRefGoogle Scholar
  14. 14.
    Burmeister LA, Ganguli M, Dodge HH, Toczek T, DeKosky ST, Nebes RD. Hypothyroidism and cognition: preliminary evidence for a specific defect in memory. Thyroid. 2001;11(12):1177–85.CrossRefGoogle Scholar
  15. 15.
    Samuels MH, Kolobova I, Smeraglio A, Peters D, Janowsky JS, Schuff KG. The effects of levothyroxine replacement or suppressive therapy on health status, mood, and cognition. J Clin Endocrinol Metab. 2014;99(3):843–51.CrossRefGoogle Scholar
  16. 16.
    Samuels MH, Kolobova I, Niederhausen M, Janowsky JS, Schuff KG. Effects of altering levothyroxine (L-T4) doses on quality of life, mood, and cognition in L-T4 treated subjects. J Clin Endocrinol Metab. 2018;103(5):1997–2008.CrossRefGoogle Scholar
  17. 17.
    Botella-Carretero JI, Galán JM, Caballero C, Sancho J, Escobar-Morreale HF. Quality of life and psychometric functionality in patients with differentiated thyroid carcinoma. Endocr Relat Cancer. 2003;10(4):601–10.CrossRefGoogle Scholar
  18. 18.
    Bunevicius R, Prange AJ. Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism. Int J Neuropsychopharmacol. 2000;3(2):167–74.CrossRefGoogle Scholar
  19. 19.
    Constant EL, Adam S, Seron X, Bruyer R, Seghers A, Daumerie C. Anxiety and depression, attention, and executive functions in hypothyroidism. J Int Neuropsychol Soc. 2005;11(5):535–44.CrossRefGoogle Scholar
  20. 20.
    Husson O, Haak HR, Buffart LM, Nieuwlaat WA, Oranje WA, Mols F, et al. Health-related quality of life and disease specific symptoms in long-term thyroid cancer survivors: a study from the population-based PROFILES registry. Acta Oncol. 2013;52(2):249–58.CrossRefGoogle Scholar
  21. 21.
    Jaracz J, Kucharska A, Rajewska-Rager A, Lacka K. Cognitive functions and mood during chronic thyrotropin-suppressive therapy with L-thyroxine in patients with differentiated thyroid carcinoma. J Endocrinol Investig. 2012;35(8):760–5.Google Scholar
  22. 22.
    Jung MS, Visovatti M. Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma. Support Care Cancer. 2017;25(3):915–23.CrossRefGoogle Scholar
  23. 23.
    Moon JH, Ahn S, Seo J, Han JW, Kim KM, Choi SH, et al. The effect of long-term thyroid-stimulating hormone suppressive therapy on the cognitive function of elderly patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2014;99(10):3782–9.CrossRefGoogle Scholar
  24. 24.
    Li M, Caeyenberghs K. Longitudinal assessment of chemotherapy-induced changes in brain and cognitive functioning: a systematic review. Neurosci Biobehav Rev. 2018;92:304–17.  https://doi.org/10.1016/j.neubiorev.2018.05.019.CrossRefGoogle Scholar
  25. 25.
    Pierson C, Waite E, Pyykkonen B. A meta-analysis of the neuropsychological effects of chemotherapy in the treatment of childhood cancer. Pediatr Blood Cancer. 2016;63(11):1998–2003.CrossRefGoogle Scholar
  26. 26.
    Edelstein K, D’agostino N, Bernstein LJ, Nathan PC, Greenberg ML, Hodgson DC, et al. Long-term neurocognitive outcomes in young adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2011;33(6):450–8.CrossRefGoogle Scholar
  27. 27.
    Zer A, Pond GR, Razak ARA, Tirona K, Gan HK, Chen EX, et al. Association of neurocognitive deficits with radiotherapy or chemoradiotherapy for patients with head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2018;144:71–9.Google Scholar
  28. 28.
    Harrison RA, Wefel JS. Neurocognitive function in adult cancer patients. Neurol Clin. 2018;36(3):653–74.CrossRefGoogle Scholar
  29. 29.
    Lee PE, Tierney MC, Wu W, Pritchard KI, Rochon PA. Endocrine treatment-associated cognitive impairment in breast cancer survivors: evidence from published studies. Breast Cancer Res Treat. 2016;158(3):407–20.CrossRefGoogle Scholar
  30. 30.
    Mandelblatt JS, Small BJ, Luta G, Hurria A, Jim H, McDonald BC, et al. Cancer-related cognitive outcomes among older breast cancer survivors in the thinking and living with cancer study. J Clin Oncol. 2018;36(32):3211–22.  https://doi.org/10.1200/JCO.18.00140.CrossRefGoogle Scholar
  31. 31.
    Liao KF, Lin CL, Lai SW. Nationwide case-control study examining the association between tamoxifen use and Alzheimer’s disease in aged women with breast cancer in Taiwan. Front Pharmacol. 2017;8:612.CrossRefGoogle Scholar
  32. 32.
    Sun LM, Chen HJ, Liang JA, Kao CH. Long-term use of tamoxifen reduces the risk of dementia: a nationwide population-based cohort study. QJM. 2016;109(2):103–9.CrossRefGoogle Scholar
  33. 33.
    Sun M, Cole AP, Hanna N, Mucci LA, Berry DL, Basaria S, et al. Cognitive impairment in men with prostate cancer treated with androgen deprivation therapy: a systematic review and meta-analysis. J Urol. 2018;199(6):1417–25.CrossRefGoogle Scholar
  34. 34.
    Morote J, Tabernero ÁJ, Álvarez Ossorio JL, Ciria JP, Domínguez-Escrig JL, Vázquez F, et al. ANAMEM Investigator Group. Cognitive function in patients with prostate cancer receiving luteinizing hormone-releasing hormone analogues: a prospective, observational, multicenter study. Int J Radiat Oncol Biol Phys. 2017;98(3):590–4.CrossRefGoogle Scholar
  35. 35.
    Tae BS, Jeon BJ, Shin SH, Choi H, Bae JH, Park JY. Correlation of androgen deprivation therapy with cognitive dysfunction in patients with prostate cancer: a nationwide population-based study using the National Health Insurance Service Database. Cancer Res Treat 2018. doi:  https://doi.org/10.4143/crt.2018.119.
  36. 36.
    Deka R, Simpson DR, Bryant AK, Nalawade V, McKay R, Murphy JD, et al. Association of androgen deprivation therapy with dementia in men with prostate cancer who receive definitive radiation therapy. JAMA Oncol. 2018;4:1616.  https://doi.org/10.1001/jamaoncol.2018.4423.CrossRefGoogle Scholar
  37. 37.
    McHugh DJ, Root JC, Nelson CJ, Morris MJ. Androgen-deprivation therapy, dementia, and cognitive dysfunction in men with prostate cancer: how much smoke and how much fire? Cancer. 2018;124(7):1326–34.CrossRefGoogle Scholar
  38. 38.
    Nead KT, Gaskin G, Chester C, Swisher-McClure S, Leeper NJ, Shah NH. Association between androgen deprivation therapy and risk of dementia. JAMA Oncol. 2017;3:49–55.CrossRefGoogle Scholar
  39. 39.
    Kao LT, Lin HC, Chung SD, Huang CY. No increased risk of dementia in patients receiving androgen deprivation therapy for prostate cancer: a 5-year follow-up study. Asian J Androl. 2017;19(4):414–7.CrossRefGoogle Scholar
  40. 40.
    Chung S, Lin H, Tsai M, Kao L, Huang C, Chen KC. Androgen deprivation therapy did not increase the risk of Alzheimer’s and Parkinson’s disease in patients with prostate cancer. Andrology. 2016;4:481–5.CrossRefGoogle Scholar
  41. 41.
    Khosrow-Khavar F, Rej S, Yin H, Aprikian A, Azoulay L. Androgen deprivation therapy and the risk of dementia in patients with prostate cancer. J Clin Oncol. 2017;35:201–7.CrossRefGoogle Scholar
  42. 42.
    Rieben C, Segna D, da Costa BR, Collet TH, Chaker L, Aubert CE, et al. Subclinical thyroid dysfunction and the risk of cognitive decline: a meta-analysis of prospective cohort studies. J Clin Endocrinol Metab. 2016;101(12):4945–54.CrossRefGoogle Scholar
  43. 43.
    Aubert CE, Bauer DC, da Costa BR, Feller M, Rieben C, Simonsick EM, et al. The association between subclinical thyroid dysfunction and dementia: The Health, Aging and Body Composition (Health ABC) Study. Clin Endocrinol. 2017;87(5):617–26.CrossRefGoogle Scholar
  44. 44.
    Szlejf C, Suemoto CK, Santos IS, Lotufo PA, Haueisen Sander Diniz MF, Barreto SM, et al. Thyrotropin level and cognitive performance: baseline results from the ELSA-Brasil study. Psychoneuroendocrinology. 2018;87:152–8.CrossRefGoogle Scholar
  45. 45.
    Peterson SJ, Cappola AR, Castro MR, Dayan CM, Farwell AP, Hennessey JV, et al. An online survey of hypothyroid patients demonstrates prominent dissatisfaction. Thyroid. 2018;28(6):707–21.CrossRefGoogle Scholar
  46. 46.
    Regalbuto C, Maiorana R, Alagona C, Paola RD, Cianci M, Alagona G, et al. Effects of either LT4 monotherapy or LT4/LT3 combined therapy in patients totally thyroidectomized for thyroid cancer. Thyroid. 2007;17(4):323–31.CrossRefGoogle Scholar
  47. 47.
    Andreotti C, Root JC, Schagen SB, McDonald BC, Saykin AJ, Atkinson TM, et al. Reliable change in neuropsychological assessment of breast cancer survivors. Psychooncology. 2016;25(1):43–50.CrossRefGoogle Scholar
  48. 48.
    Edelstein K, Bernstein LJ. Cognitive dysfunction after chemotherapy for breast cancer. J Int Neuropsychol Soc. 2014;20(4):351–6.CrossRefGoogle Scholar
  49. 49.
    Higgins JPT, Green S. 2011 Recommendations for testing of funnel plot asymmetry. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 Available at: http://handbook-5-1.cochrane.org/chapter_10/10_4_3_1_recommendations_on_testing_for_funnel_plot_asymmetry.htm Accessed January 31, 2019.
  50. 50.
    Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12(7):703–8.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Omar Saeed
    • 1
    • 2
  • Lori J. Bernstein
    • 3
  • Rouhi Fazelzad
    • 4
  • Mary Samuels
    • 5
  • Lynn A. Burmeister
    • 6
  • Lehana Thabane
    • 7
  • Shereen Ezzat
    • 8
  • David P. Goldstein
    • 9
  • Jennifer Jones
    • 3
  • Anna M. Sawka
    • 2
    • 10
    Email author
  1. 1.Division of EndocrinologySt. Michael’s HospitalTorontoCanada
  2. 2.Division of EndocrinologyUniversity of TorontoTorontoCanada
  3. 3.Department of Supportive Care and Department of PsychiatryUniversity Health Network and University of TorontoTorontoCanada
  4. 4.Princess Margaret Cancer CentreUniversity Health Network Library and Information ServicesTorontoCanada
  5. 5.Division of Endocrinology, Diabetes and Clinical NutritionOregon Health and Science UniversityPortlandUSA
  6. 6.Division of Diabetes, Endocrinology, and MetabolismUniversity of MinnesotaMinneapolisUSA
  7. 7.Department of Health Research Methods, Evidence, and ImpactMcMaster UniversityHamiltonCanada
  8. 8.Department of Endocrine OncologyPrincess Margaret Cancer Centre and University of TorontoTorontoCanada
  9. 9.Department of Otolaryngology, Head and Neck SurgeryUniversity Health Network and University of TorontoTorontoCanada
  10. 10.Division of EndocrinologyUniversity Health Network (Toronto General Hospital)TorontoCanada

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