Brain Tumor Res Treat.  2025 Jan;13(1):1-16. 10.14791/btrt.2024.0033.

Cognitive Rehabilitation of Brain Tumor Survivors: A Systematic Review

• Tariq R
• Aziz HF
• Paracha S
• Zahid N
• Ainger TJ
• Mirza FA
• Enam SA

• KMID: 2565044
• DOI: http://doi.org/10.14791/btrt.2024.0033

Abstract

Background
Cognitive decline is commonly seen in brain tumor (BT) patients and is associated with a worsened prognosis. Cognitive rehabilitation (CR) for cancer-related cognitive dysfunction has been widely studied for non-central nervous system cancers; however, recent emerging research has commenced documenting CR strategies for BT patients and survivors. Our objective was to review the current literature on various CR modalities in patients and BT survivors.
Methods
The review was conducted in accordance with the PRISMA guidelines. The studies on CR were searched across 3 databases using a predefined search strategy. After removing duplicates, performing initial and full-text screenings, and applying inclusion criteria, relevant articles were selected. The demographic details, CR technique, cognitive tasks/tests administered, cognitive functions assessed, follow-up time, and outcomes of the intervention were assessed.
Results
A total of 15 studies were included in the review. Neuropsychologist-guided training sessions to improve memory, attention, and executive functioning are effective in improving the mentioned domains. Younger and more educated patients benefited the most. Holistic mnemonic training and neurofeedback were not shown to affect overall cognitive functioning. Computer-based training programs showed improvements in executive functions of pediatric BT survivors, however, feasibility studies showed conflicting results. Aerobic exercises improved executive functions and decreased symptoms of the tumor. Both yoga and combined aerobic and strength training improved overall cognitive functioning. Active video gaming may improve motor and process skills; however, no effect was seen on cognitive functioning.
Conclusion
Neuropsychologic training, computer-based programs, and physical exercise have been found effective in improving or preventing decline in cognitive functions of BT patients. Given the limited trials and methodological variations, a standardized CR program cannot be established at present. Ongoing trials are expected to provide valuable data in the near future.

Keyword

Brain tumors; Cognitive functions; Cognitive rehabilitation

Figure

• 

  Fig. 1 PRISMA flowchart. BTs, brain tumors; QoL, quality of life.

Reference

1. Hassler MR, Elandt K, Preusser M, Lehrner J, Binder P, Dieckmann K, et al. Neurocognitive training in patients with high-grade glioma: a pilot study. J Neurooncol. 2010; 97:109–115. PMID: 19763790.

2. Tucha O, Smely C, Preier M, Lange KW. Cognitive deficits before treatment among patients with brain tumors. Neurosurgery. 2000; 47:324–333. discussion 333-4. PMID: 10942005.

3. Kapoor I, Prabhakar H, Mahajan C. Postoperative cognitive dysfunction. Indian J Crit Care Med. 2019; 23(Suppl 2):S162–S164. PMID: 31485127.

4. Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, et al. 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. 2016; 316:401–409. PMID: 27458945.

5. Douw L, Klein M, Fagel SS, van den Heuvel J, Taphoorn MJ, Aaronson NK, et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol. 2009; 8:810–818. PMID: 19665931.

6. Cramer CK, Cummings TL, Andrews RN, Strowd R, Rapp SR, Shaw EG, et al. Treatment of radiation-induced cognitive decline in adult brain tumor patients. Curr Treat Options Oncol. 2019; 20:42. PMID: 30963289.

7. Taphoorn MJ, Klein M. Cognitive deficits in adult patients with brain tumours. Lancet Neurol. 2004; 3:159–168. PMID: 14980531.

8. Udaka YT, Packer RJ. Pediatric brain tumors. Neurol Clin. 2018; 36:533–556. PMID: 30072070.

9. Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015–2019. Neuro Oncol. 2022; 24(Suppl 5):v1–v95. PMID: 36196752.

10. Duffner PK. Risk factors for cognitive decline in children treated for brain tumors. Eur J Paediatr Neurol. 2010; 14:106–115. PMID: 19931477.

11. Oyefiade A, Paltin I, De Luca CR, Hardy KK, Grosshans DR, Chintagumpala M, et al. Cognitive risk in survivors of pediatric brain tumors. J Clin Oncol. 2021; 39:1718–1726. PMID: 33886348.

12. Bruhn H, Blystad I, Milos P, Malmström A, Dahle C, Vrethem M, et al. Initial cognitive impairment predicts shorter survival of patients with glioblastoma. Acta Neurol Scand. 2022; 145:94–101. PMID: 34514585.

13. van Kessel E, Huenges Wajer IMC, Ruis C, Seute T, Fonville S, De Vos FYFL, et al. Cognitive impairments are independently associated with shorter survival in diffuse glioma patients. J Neurol. 2021; 268:1434–1442. PMID: 33211158.

14. Tariq R, Hussain N, Baqai MWS. Factors affecting cognitive functions of patients with high-grade gliomas: a systematic review. Neurol Sci. 2023; 44:1917–1929. PMID: 36773209.

15. Scheibel RS, Meyers CA, Levin VA. Cognitive dysfunction following surgery for intracerebral glioma: influence of histopathology, lesion location, and treatment. J Neurooncol. 1996; 30:61–69. PMID: 8865004.

16. Hahn CA, Dunn RH, Logue PE, King JH, Edwards CL, Halperin EC. Prospective study of neuropsychologic testing and quality-of-life assessment of adults with primary malignant brain tumors. Int J Radiat Oncol Biol Phys. 2003; 55:992–999. PMID: 12605978.

17. Murphy C, Upshaw NC, Thomas AS, Fong G, Janss A, Mazewski C, et al. Impact of executive functioning on health-related quality of life of pediatric brain tumor survivors. Pediatr Blood Cancer. 2021; 68:e29130. PMID: 34047487.

18. Cheung AT, Li WHC, Ho LLK, Ho KY, Chiu SY, Chan CG, et al. Impact of brain tumor and its treatment on the physical and psychological well-being, and quality of life amongst pediatric brain tumor survivors. Eur J Oncol Nurs. 2019; 41:104–109. PMID: 31358242.

19. Rimmer B, Bolnykh I, Dutton L, Lewis J, Burns R, Gallagher P, et al. Health-related quality of life in adults with low-grade gliomas: a systematic review. Qual Life Res. 2023; 32:625–651. PMID: 35931881.

20. Cramer CK, McKee N, Case LD, Chan MD, Cummings TL, Lesser GJ, et al. Mild cognitive impairment in long-term brain tumor survivors following brain irradiation. J Neurooncol. 2019; 141:235–244. PMID: 30406339.

21. Gilhus NE, Brainin M, Barnes MP. European handbook of neurological management. 2nd ed. Chichester: Wiley-Blackwell;2011.

22. Fernandes HA, Richard NM, Edelstein K. Cognitive rehabilitation for cancer-related cognitive dysfunction: a systematic review. Support Care Cancer. 2019; 27:3253–3279. PMID: 31147780.

23. Fraley CE, Thigpen JC, Pearson MM, Kuttesch JF Jr, Desjardins L, Hoskinson KR, et al. Predictors of cognitive function in pediatric brain tumor patients: pre-surgery through 24-month follow-up. Appl Neuropsychol Child. 2021; 10:340–347. PMID: 31887256.

24. Gehring K, Sitskoorn MM, Gundy CM, Sikkes SA, Klein M, Postma TJ, et al. Cognitive rehabilitation in patients with gliomas: a randomized, controlled trial. J Clin Oncol. 2009; 27:3712–3722. PMID: 19470928.

25. Gehring K, Aaronson NK, Gundy CM, Taphoorn MJ, Sitskoorn MM. Predictors of neuropsychological improvement following cognitive rehabilitation in patients with gliomas. J Int Neuropsychol Soc. 2011; 17:256–266. PMID: 21205412.

26. Locke DE, Cerhan JH, Wu W, Malec JF, Clark MM, Rummans TA, et al. Cognitive rehabilitation and problem-solving to improve quality of life of patients with primary brain tumors: a pilot study. J Support Oncol. 2008; 6:383–391. PMID: 19149323.

27. Richard NM, Bernstein LJ, Mason WP, Laperriere N, Maurice C, Millar BA, et al. Cognitive rehabilitation for executive dysfunction in brain tumor patients: a pilot randomized controlled trial. J Neurooncol. 2019; 142:565–575. PMID: 30847839.

28. de Ruiter MA, Oosterlaan J, Schouten-van Meeteren AY, Maurice-Stam H, van Vuurden DG, Gidding C, et al. Neurofeedback ineffective in paediatric brain tumour survivors: results of a double-blind randomised placebo-controlled trial. Eur J Cancer. 2016; 64:62–73. PMID: 27343714.

29. Carlson-Green B, Puig J, Bendel A. Feasibility and efficacy of an extended trial of home-based working memory training for pediatric brain tumor survivors: a pilot study. Neurooncol Pract. 2017; 4:111–120. PMID: 31385985.

30. Hocking MC, Paltin I, Quast LF, Barakat LP. Acceptability and feasibility in a pilot randomized clinical trial of computerized working memory training and parental problem-solving training with pediatric brain tumor survivors. J Pediatr Psychol. 2019; 44:669–678. PMID: 30874803.

31. Sabel M, Sjölund A, Broeren J, Arvidsson D, Saury JM, Gillenstrand J, et al. Effects of physically active video gaming on cognition and activities of daily living in childhood brain tumor survivors: a randomized pilot study. Neurooncol Pract. 2017; 4:98–110. PMID: 31385977.

32. van der Linden SD, Sitskoorn MM, Rutten GM, Gehring K. Feasibility of the evidence-based cognitive telerehabilitation program remind for patients with primary brain tumors. J Neurooncol. 2018; 137:523–532. PMID: 29322428.

33. van der Linden SD, Rutten GM, Dirven L, Taphoorn MJB, Satoer DD, Dirven CMF, et al. eHealth cognitive rehabilitation for brain tumor patients: results of a randomized controlled trial. J Neurooncol. 2021; 154:315–326. PMID: 34487313.

34. Zucchella C, Capone A, Codella V, De Nunzio AM, Vecchione C, Sandrini G, et al. Cognitive rehabilitation for early post-surgery inpatients affected by primary brain tumor: a randomized, controlled trial. J Neurooncol. 2013; 114:93–100. PMID: 23677749.

35. Cox E, Bells S, Timmons BW, Laughlin S, Bouffet E, de Medeiros C, et al. A controlled clinical crossover trial of exercise training to improve cognition and neural communication in pediatric brain tumor survivors. Clin Neurophysiol. 2020; 131:1533–1547. PMID: 32403066.

36. Dülger E, Mut M, Erbas T, Sahiner L, Vardar Yağlı N, Bilgin S. Effects of combined aerobic-strength training and yoga on quality of life and related parameters in women with pituitary adenoma after surgery: a randomized crossover study. Eur J Endocrinol. 2022; 186:667–675. PMID: 35380988.

37. Gehring K, Stuiver MM, Visser E, Kloek C, van den Bent M, Hanse M, et al. A pilot randomized controlled trial of exercise to improve cognitive performance in patients with stable glioma: a proof of concept. Neuro Oncol. 2020; 22:103–115. PMID: 31755917.

38. Hansen A, Pedersen CB, Jarden JO, Beier D, Minet LR, Søgaard K. Effectiveness of physical therapy– and occupational therapy–based rehabilitation in people who have glioma and are undergoing active anticancer treatment: single-blind, randomized controlled trial. Phys Ther. 2020; 100:564–574. PMID: 32043148.

39. Cicerone KD, Goldin Y, Ganci K, Rosenbaum A, Wethe JV, Langenbahn DM, et al. Evidence-based cognitive rehabilitation: systematic review of the literature from 2009 through 2014. Arch Phys Med Rehabil. 2019; 100:1515–1533. PMID: 30926291.

40. Irazoki E, Contreras-Somoza LM, Toribio-Guzmán JM, Jenaro-Río C, van der Roest H, Franco-Martín MA. Technologies for cognitive training and cognitive rehabilitation for people with mild cognitive impairment and dementia. A systematic review. Front Psychol. 2020; 11:648. PMID: 32373018.

41. Loetscher T, Potter KJ, Wong D, das Nair R. Cognitive rehabilitation for attention deficits following stroke. Cochrane Database Syst Rev. 2019; 2019:CD002842. PMID: 31706263.

42. Chen MH, Chiaravalloti ND, DeLuca J. Neurological update: cognitive rehabilitation in multiple sclerosis. J Neurol. 2021; 268:4908–4914. PMID: 34028615.

43. Anderson SW, Damasio H, Tranel D. Neuropsychological impairments associated with lesions caused by tumor or stroke. Arch Neurol. 1990; 47:397–405. PMID: 2322133.

44. Hui CL, Lam BS, Wong AK, Tao TJ, Ho EC, Suen YN, et al. ReMind, a smartphone application for psychotic relapse prediction: a longitudinal study protocol. Early Interv Psychiatry. 2021; 15:1659–1666. PMID: 33369162.

45. Chaudhry BM, Smith J. RefineMind: a mobile app for people with dementia and their caregivers. Chandra Kruse L, Seidel S, Hausvik GI, editors. The next wave of sociotechnical design. DESRIST 2021. Lecture Notes in Computer Science, vol 12807. Cham: Springer;2021. p. 16–21.

46. Reddick WE, White HA, Glass JO, Wheeler GC, Thompson SJ, Gajjar A, et al. Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors. Cancer. 2003; 97:2512–2519. PMID: 12733151.

47. Sciancalepore F, Tariciotti L, Remoli G, Menegatti D, Carai A, Petruzzellis G, et al. Computer-based cognitive training in children with primary brain tumours: a systematic review. Cancers (Basel). 2022; 14:3879. PMID: 36010873.

48. Cormie P, Nowak AK, Chambers SK, Galvão DA, Newton RU. The potential role of exercise in neuro-oncology. Front Oncol. 2015; 5:85. PMID: 25905043.

49. Khaleqi-Sohi M, Sadria G, Ghalibafian M, Khademi-Kalantari K, Irannejad S. The effects of physical activity and exercise therapy on pediatric brain tumor survivors: a systematic review. J Bodyw Mov Ther. 2022; 30:1–9. PMID: 35500954.

50. Grieve SM, Williams LM, Paul RH, Clark CR, Gordon E. Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging study. AJNR Am J Neuroradiol. 2007; 28:226–235. PMID: 17296985.

51. Williams MS, Shellenberger S. How does your engine run?: a leader’s guide to the alert program for self-regulation. Albuquerque: TherapyWorks, Inc.;1996.

52. He F, Huang H, Ye L, Wen X, Cheng ASK. Meta-analysis of neurocognitive rehabilitation for cognitive dysfunction among pediatric cancer survivors. J Cancer Res Ther. 2022; 18:2058–2065. PMID: 36647970.

53. Dadario NB, Young IM, Zhang X, Teo C, Doyen S, Sughrue ME. Prehabilitation and rehabilitation using data-driven, parcel-guided transcranial magnetic stimulation treatment for brain tumor surgery: proof of concept case report. Brain Netw Modul. 2022; 1:48–56.

54. Gehring K, Patwardhan SY, Collins R, Groves MD, Etzel CJ, Meyers CA, et al. A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor. J Neurooncol. 2012; 107:165–174. PMID: 21964738.

55. Boele FW, Douw L, de Groot M, van Thuijl HF, Cleijne W, Heimans JJ, et al. The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial. Neuro Oncol. 2013; 15:1420–1428. PMID: 23925452.

56. Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013; 15:1429–1437. PMID: 23956241.

57. Diansari Y, Harun Y, Marisdina S, Felistia Y. P05.01 the efficacy of donepezil on cognitive function in postoperative brain tumor patients. Neuro Oncol. 2019; 21(Supplement 3):iii33–iii34.

58. University Health Network, Toronto. Cognitive rehabilitation in brain tumor patients after neurosurgery. ClinicalTrials.gov [Internet]. Bethesda: U.S. National Library of Medicine;2014. updated Sep 25, 2018. Accessed June 19, 2023. at https://clinicaltrials.gov/study/NCT02489071.

59. Ziekenhuis ET. Cognitive rehabilitation in brain tumor patients after neurosurgery. ClinicalTrials.gov [Internet]. Bethesda: U.S. National Library of Medicine;2015. updated Feb 12, 2018. Accessed June 19, 2023. at https://clinicaltrials.gov/study/NCT03373487.

60. Gehring K. Cognitive rehabilitation in brain tumor patients after neurosurgery. International Clinical Trials Registry Platform [Internet]. Geneva: World Health Organization;2015. updated Feb 28, 2024. Accessed June 19, 2023. at https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON29674.

61. Children’s Oncology Group. Computer training program for younger patients with a brain tumor who underwent radiation therapy. ClinicalTrials.gov [Internet]. Bethesda: U.S. National Library of Medicine;2015. updated Oct 18, 2024. Accessed June 19, 2023. at https://clinicaltrials.gov/study/NCT01503086.

62. The Hong Kong Polytechnic University. Musical training programme to improve neurocognitive functioning of children surviving brain tumours. ClinicalTrials.gov [Internet]. Bethesda: U.S. National Library of Medicine;2021. updated Jul 29, 2024. Accessed June 19, 2023. at https://clinicaltrials.gov/study/NCT05202925.

63. Vanderbilt University. Neuroplasticity-based cognitive remediation for pediatric brain tumor survivors (CRPBT). ClinicalTrials.gov [Internet]. Bethesda: U.S. National Library of Medicine;2014. updated Sep 4, 2018. Accessed June 19, 2023. at https://clinicaltrials.gov/study/NCT02129712.

64. University of California, San Francisco. Rehabilitation and longitudinal follow-up of cognition in adult lower grade gliomas. ClinicalTrials.gov [Internet]. Bethesda: U.S. National Library of Medicine;2022. updated Feb 23, 2024. Accessed June 19, 2023. at https://clinicaltrials.gov/study/NCT03948490.

65. National Cancer Institute (NCI). Trial evaluating an enhanced physical activity intervention to improve cognitive late effects in children treated with cranial radiation for brain tumors. ClinicalTrials.gov [Internet]. Bethesda: U.S. National Library of Medicine;2014. updated Nov 8, 2024. Accessed June 19, 2023. at https://clinicaltrials.gov/study/NCT02153957.