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Mild cognitive impairment in long-term brain tumor survivors following brain irradiation

  • Clinical Study
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Abstract

Introduction

There is no accepted classification of cognitive impairment in cancer survivors. We assess the extent of mild cognitive impairment (MCI) syndrome in brain tumor survivors using criteria adapted from the National Institute on Aging and the Alzheimer’s Association (NIA-AA).

Methods

We retrospectively reviewed the cognitive data of brain tumor survivors post-radiation therapy (RT) enrolled from 2008 to 2011 in a randomized trial of donepezil versus placebo for cognitive impairment. One hundred and ninety eight adult survivors with primary or metastatic brain tumors who were ≥ 6 months post RT were recruited at 24 sites in the United States. Cognitive function was assessed at baseline, 12 and 24 weeks post-randomization. For this analysis, we used baseline data to identify MCI and possible dementia using adapted NIA-AA criteria. Cases were subtyped into four groups: amnestic MCI-single domain (aMCI-sd), amnestic MCI-multiple domain (aMCI-md), non-amnestic MCI-single domain (naMCI-sd), and non-amnestic MCI-multiple domain (naMCI-md).

Results

One hundred and thirty one of 197 evaluable patients (66%) met criteria for MCI. Of these, 13% were classified as aMCI-sd, 58% as aMCI-md, 19% as naMCI-sd, and 10% as naMCI-md. Patients with poorer performance status, less education, lower household income and those not working outside the home were more likely to be classified as MCI.

Conclusion

Two-thirds of post-RT brain tumor survivors met NIA-AA criteria for MCI. This taxonomy may be useful when applied to brain tumor survivors because it defines cognitive phenotypes that may be differentially associated with course, treatment response, and risk factor profiles.

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References

  1. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56(3):303–308

    Article  CAS  PubMed  Google Scholar 

  2. Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de LM, DeCarli, Erkinjuntti C, Giacobini T, Graff E, Hardy C, Jack J, Jorm C, Ritchie A, K, van DC, Visser, Petersen P RC (2004) Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256(3):240–246

    Article  CAS  PubMed  Google Scholar 

  3. Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256(3):183–194. https://doi.org/10.1111/j.1365-2796.2004.01388.x

    Article  CAS  PubMed  Google Scholar 

  4. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):270–279. https://doi.org/10.1016/j.jalz.2011.03.008

    Article  PubMed  PubMed Central  Google Scholar 

  5. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):263–269. https://doi.org/10.1016/j.jalz.2011.03.005

    Article  PubMed  PubMed Central  Google Scholar 

  6. McKhann G, Drachman D, Folstein MF, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944

    Article  CAS  PubMed  Google Scholar 

  7. American Psychiatric Association, American Psychiatric Association. Task Force on DSM-IV (1994) Diagnostic and statistical manual of mental disorders: DSM-IV. 4th edn. American Psychiatric Association, Washington, DC

    Google Scholar 

  8. Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2017) CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro-Oncology 19(suppl_5):v1–v88. https://doi.org/10.1093/neuonc/nox158

    Article  Google Scholar 

  9. Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD (2012) Radiation-induced brain injury: a review. Front Oncol 2:73. https://doi.org/10.3389/fonc.2012.00073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316(4):401–409. https://doi.org/10.1001/jama.2016.9839

    Article  PubMed  PubMed Central  Google Scholar 

  11. Peiffer AM, Leyrer CM, Greene-Schloesser DM, Shing E, Kearns WT, Hinson WH, Tatter SB, Ip EH, Rapp SR, Robbins ME, Shaw EG, Chan MD (2013) Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline. Neurology 80(8):747–753. https://doi.org/10.1212/WNL.0b013e318283bb0a

    Article  PubMed  PubMed Central  Google Scholar 

  12. Douw L, Klein M, Fagel SS, van den Heuvel J, Taphoorn MJ, Aaronson NK, Postma TJ, Vandertop WP, Mooij JJ, Boerman RH, Beute GN, Sluimer JD, Slotman BJ, Reijneveld JC, Heimans JJ (2009) Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 8(9):810–818. https://doi.org/10.1016/S1474-4422(09)70204-2

    Article  PubMed  Google Scholar 

  13. Armstrong TS, Wefel JS, Wang M, Won M, Bottomley A, Mendoza TR, Coens C, Werner-Wasik M, Brachman D, Choucair AK, Gilbert MR (2011) Clinical utility of neurocognitive function (NCF), quality of life (QOL), and symptom assessment as prognostic factors for survival and measures of treatment effects on RTOG 0525. J Clin Oncol 29(15_suppl):2016–2016. https://doi.org/10.1200/jco.2011.29.15_suppl.2016

    Article  Google Scholar 

  14. Meyers CA, Weitzner MA, Valentine AD, Levin VA (1998) Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J Clin Oncol 16(7):2522–2527. https://doi.org/10.1200/JCO.1998.16.7.2522

    Article  CAS  PubMed  Google Scholar 

  15. Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, Choucair A, Fox S, Suh JH, Roberge D, Kavadi V, Bentzen SM, Mehta MP, Watkins-Bruner D, Radiation Therapy Oncology G (2013) Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-Oncology 15(10):1429–1437. https://doi.org/10.1093/neuonc/not114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Attia A, Rapp SR, Case LD, D’Agostino R, Lesser G, Naughton M, McMullen K, Rosdhal R, Shaw EG (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. https://doi.org/10.1007/s11060-012-0901-9

    Article  PubMed  PubMed Central  Google Scholar 

  17. Butler JM Jr, Case LD, Atkins J, Frizzell B, Sanders G, Griffin P, Lesser G, McMullen K, McQuellon R, Naughton M, Rapp S, Stieber V, Shaw EG (2007) A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. Int J Radiat Oncol Biol Phys 69(5):1496–1501. https://doi.org/10.1016/j.ijrobp.2007.05.076

    Article  CAS  PubMed  Google Scholar 

  18. Rapp SR, Case LD, Peiffer A, Naughton MM, Chan MD, Stieber VW, Moore DF Jr, Falchuk SC, Piephoff JV, Edenfield WJ, Giguere JK, Loghin ME, Shaw EG (2015) Donepezil for irradiated brain tumor survivors: a phase III randomized placebo-controlled clinical trial. J Clin Oncol 33(15):1653–1659. https://doi.org/10.1200/JCO.2014.58.4508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R, Contributors (2018) NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14(4):535–562. https://doi.org/10.1016/j.jalz.2018.02.018

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gifford AR, Lawrence JA, Baker LD, Balcueva EP, Case D, Craft S, Curtis AE, Griffin L, Groteluschen DL, Klepin HD, Lesser GJ, Messino MJ, Naughton M, Samuel TA, Rapp S, Sachs B, Sink KM, Williamson J, Shaw EG (2017) National Institute on Aging /Alzheimer’s Association criteria for Mild Cognitive Impairment applied to chemotherapy treated breast cancer survivors. J Oncol Res 1(1):1–19

    Article  Google Scholar 

  21. Weitzner MA, Meyers CA, Gelke CK, Byrne KS, Cella DF, Levin VA (1995) The functional assessment of cancer therapy (FACT) scale. Development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors. Cancer 75(5):1151–1161

    Article  CAS  PubMed  Google Scholar 

  22. Brandt J (1991) The hopkins verbal learning test: Development of a new memory test with six equivalent forms. Clin Neuropsychol 5(2):125–142. https://doi.org/10.1080/13854049108403297

    Article  Google Scholar 

  23. Reitan RM (1958) Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skills 8(3):271–276. https://doi.org/10.2466/pms.1958.8.3.271

    Article  Google Scholar 

  24. Wechsler D (1996) The Wechsler memory scale (WMS-III), 3rd edn. Psychological Corporation, Harcourt, Inc., San Diego

    Google Scholar 

  25. Ruff RM, Light RH, Parker SB, Levin HS (1996) Benton controlled oral word association test: reliability and updated norms. Arch Clin Neuropsychol 11(4):329–338

    Article  CAS  PubMed  Google Scholar 

  26. Webster K, Cella D, Yost K (2003) The functional assessment of chronic illness therapy (FACIT) measurement system: properties, applications, and interpretation. Health Qual Life Outcomes 1(1):79

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lawrence JA, Griffin L, Balcueva EP, Groteluschen DL, Samuel TA, Lesser GJ, Naughton MJ, Case LD, Shaw EG, Rapp SR (2016) A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy. J Cancer Surviv 10(1):176–184. https://doi.org/10.1007/s11764-015-0463-x

    Article  CAS  PubMed  Google Scholar 

  28. Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR, Ofstedal MB, Burke JR, Hurd MD, Potter GG, Rodgers WL, Steffens DC, McArdle JJ, Willis RJ, Wallace RB (2008) Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med 148(6):427–434

    Article  PubMed  PubMed Central  Google Scholar 

  29. Petersen RC, Roberts RO, Knopman DS, Geda YE, Cha RH, Pankratz VS, Boeve BF, Tangalos EG, Ivnik RJ, Rocca WA (2010) Prevalence of mild cognitive impairment is higher in men The Mayo Clinic Study of Aging. Neurology 75(10):889–897. doi:https://doi.org/10.1212/WNL.0b013e3181f11d85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lopez OL, Jagust WJ, DeKosky ST, Becker JT, Fitzpatrick A, Dulberg C, Breitner J, Lyketsos C, Jones B, Kawas C, Carlson M, Kuller LH (2003) Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol 60(10):1385–1389

    Article  PubMed  Google Scholar 

  31. Knopman DS, Gottesman RF, Sharrett AR, Wruck LM, Windham BG, Coker L, Schneider AL, Hengrui S, Alonso A, Coresh J, Albert MS, Mosley TH Jr (2016) Mild cognitive impairment and dementia prevalence: the atherosclerosis risk in communities neurocognitive study (ARIC-NCS). Alzheimers Dement (Amst) 2:1–11. https://doi.org/10.1016/j.dadm.2015.12.002

    Article  Google Scholar 

  32. Grundman M, Petersen RC, Ferris SH, Thomas RG, Aisen PS, Bennett DA, Foster NL, Jack CR Jr, Galasko DR, Doody R, Kaye J, Sano M, Mohs R, Gauthier S, Kim HT, Jin S, Schultz AN, Schafer K, Mulnard R, van Dyck CH, Mintzer J, Zamrini EY, Cahn-Weiner D, Thal LJ (2004) Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol 61(1):59–66. https://doi.org/10.1001/archneur.61.1.59

    Article  PubMed  Google Scholar 

  33. Ahles TA, Saykin AJ, Noll WW, Furstenberg CT, Guerin S, Cole B, Mott LA (2003) The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy. Psychooncology 12(6):612–619

    Article  PubMed  Google Scholar 

  34. Rapp SR, Legault C, Henderson VW, Brunner RL, Masaki K, Jones B, Absher J, Thal L (2010) Subtypes of mild cognitive impairment in older postmenopausal women: the Women’s Health Initiative Memory Study. Alzheimer Dis Assoc Disord 24(3):248–255. https://doi.org/10.1097/WAD.0b013e3181d715d5

    Article  PubMed  PubMed Central  Google Scholar 

  35. Okoukoni C, McTyre ER, Ayala Peacock DN, Peiffer AM, Strowd R, Cramer C, Hinson WH, Rapp S, Metheny-Barlow L, Shaw EG, Chan MD (2017) Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation. Adv Radiat Oncol 2(4):624–629. https://doi.org/10.1016/j.adro.2017.08.013

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by Grant No. 5R01NR009675-04 (PI Stephen R. Rapp) from the National Institute of Nursing Research, Grant No. 2 U10 CA 81851-09-13 from the National Cancer Institute Division of Cancer Prevention to the Wake Forest Clinical Community Oncology Program, Grant No. 1UG CA189824-01 from the National Institutes of Health/National Cancer Institute to the Wake Forest NCORP Research Base and Eisai Inc.

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Contributions

All of the authors contributed substantial time and intellectual effort in producing this manuscript, including: experimental design (CKC, SRR, LDC, EGS, NM, MDC); data analysis and statistics (LDC, SRR, CKC, NM, TLC); data interpretation (CKC, SRR, TLC, GJL, EGS, MDC); manuscript writing (CKC, TLC, LDC, SRR, EGS, GJL, MDC, NM).

Corresponding author

Correspondence to Christina K. Cramer.

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The authors declare that they have no conflicts of interest.

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Cramer, C.K., McKee, N., Case, L.D. et al. Mild cognitive impairment in long-term brain tumor survivors following brain irradiation. J Neurooncol 141, 235–244 (2019). https://doi.org/10.1007/s11060-018-03032-8

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