Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Qol and Patients' Care

Cognitive problems following hematopoietic stem cell transplant: relationships with sleep, depression and fatigue

Bone Marrow Transplantation volume 52, pages 279–284 (2017)Cite this article

Subjects

Abstract

Cognitive problems are a significant, persistent concern for patients undergoing hematopoietic stem cell transplant (HSCT). Sleep is important for many cognitive tasks; however, the relationship between sleep and cognitive problems for HSCT patients is unknown. This study examined the relationship between sleep and cognitive problems for HSCT patients from pre to post transplant. Patients undergoing HSCT (N=138) completed questionnaires at pre-transplant and during the 12 months following transplant. Questionnaires assessed sleep and cognitive problems as well as commonly co-occurring symptoms: depressive symptoms, fatigue and pain. Post hoc analyses examined the relationship of specific sleep problems with cognitive problems. Sleep problems covaried with cognitive problems even after controlling for depressive symptoms, fatigue and pain. Depressive symptoms and fatigue were also uniquely related to cognitive problems. Post hoc analyses suggest that sleep somnolence, shortness of breath, snoring and perceptions of inadequate sleep may contribute to the association found between sleep and cognitive problems. Findings suggest that sleep problems are associated with and may contribute to cognitive problems for HSCT patients. However, sleep problems are rarely screened for or discussed during clinic visits. Assessing and treating specific sleep problems in addition to depressive symptoms and fatigue may have implications for improving cognitive problems for HSCT patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Booth-Jones M, Jacobsen PB, Ransom S, Soety E . Characteristics and correlates of cognitive functioning following bone marrow transplantation. Bone Marrow Transplant 2005; 36: 695–702.

    Article  CAS  PubMed  Google Scholar 

  2. Harder H, Cornelissen JJ, Van Gool AR, Duivenvoorden HJ, Eijkenboom WM, van den Bent MJ . Cognitive functioning and quality of life in long-term adult survivors of bone marrow transplantation. Cancer 2002; 95: 183–192.

    Article  PubMed  Google Scholar 

  3. Meyers CA, Weitzner M, Byrne K, Valentine A, Champlin RE, Przepiorka D . Evaluation of the neurobehavioral functioning of patients before, during, and after bone marrow transplantation. J Clin Oncol 1994; 12: 820–826.

    Article  CAS  PubMed  Google Scholar 

  4. Syrjala KL, Dikmen S, Langer SL, Roth-Roemer S, Abrams JR . Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant. Blood 2004; 104: 3386–3392.

    Article  CAS  PubMed  Google Scholar 

  5. Saleh US, Brockopp DY . Quality of life one year following bone marrow transplantation: psychometric evaluation of the quality of life in bone marrow transplant survivors tool. Oncol Nurs Forum 2001; 28: 1457–1464.

    CAS  PubMed  Google Scholar 

  6. Wu LM, Austin J, Hamilton JG, Valdimarsdottir H, Isola L, Rowley S et al. Self-efficacy beliefs mediate the relationship between subjective cognitive functioning and physical and mental well-being after hematopoietic stem cell transplant. Psycho-oncology 2012; 21: 1175–1184.

    Article  PubMed  Google Scholar 

  7. Gais S, Plihal W, Wagner U, Born J . Early sleep triggers memory for early visual discrimination skills. Nat Neurosci 2000; 3: 1335–1339.

    Article  CAS  PubMed  Google Scholar 

  8. Goel N, Rao H, Durmer JS, Dinges DF . Neurocognitive consequences of sleep deprivation. Semin Neurol 2009; 29: 320–339.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Mednick SC, Makovski T, Cai DJ, Jiang YV . Sleep and rest facilitate implicit memory in a visual search task. Vision Res 2009; 49: 2557–2565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Smith C . Sleep states and memory processes in humans: procedural versus declarative memory systems. Sleep Med Rev 2001; 5: 491–506.

    Article  CAS  PubMed  Google Scholar 

  11. Stavitsky K, Neargarder S, Bogdanova Y, McNamara P, Cronin-Golomb A . The impact of sleep quality on cognitive functioning in Parkinson's disease. J Int Neuropsychol Soc 2012; 18: 108–117.

    Article  PubMed  Google Scholar 

  12. Stickgold R . Sleep-dependent memory consolidation. Nature 2005; 437: 1272–1278.

    Article  CAS  PubMed  Google Scholar 

  13. Stickgold R, Hobson JA, Fosse R, Fosse M . Sleep, learning, and dreams: off-line memory reprocessing. Science 2001; 294: 1052–1057.

    Article  CAS  PubMed  Google Scholar 

  14. Ohayon MM, Vecchierini MF . Normative sleep data, cognitive function and daily living activities in older adults in the community. Sleep 2005; 28: 981–989.

    Article  PubMed  Google Scholar 

  15. Hjelm C, Stromberg A, Arestedt K, Brostrom A . Association between sleep-disordered breathing, sleep-wake pattern, and cognitive impairment among patients with chronic heart failure. Eur J Heart Fail 2013; 15: 496–504.

    Article  PubMed  Google Scholar 

  16. Jean-Pierre P, Grandner MA, Garland SN, Henry E, Jean-Louis G, Burish TG . Self-reported memory problems in adult-onset cancer survivors: effects of cardiovascular disease and insomnia. Sleep Med 2015; 16: 845–849.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Von Ah D, Tallman EF . Perceived cognitive function in breast cancer survivors: evaluating relationships with objective cognitive performance and other symptoms using the functional assessment of cancer therapy-cognitive function instrument. J Pain Symptom Manage 2015; 49: 697–706.

    Article  PubMed  Google Scholar 

  18. Chen M-L, Yu C-T, Yang C-H . Sleep disturbances and quality of life in lung cancer patients undergoing chemotherapy. Lung Cancer 2008; 62: 391–400.

    Article  PubMed  Google Scholar 

  19. Boonstra L, Harden K, Jarvis S, Palmer S, Kavanaugh-Carveth P, Barnett J et al. Sleep disturbance in hospitalized recipients of stem cell transplantation. Clin J Oncol Nurs 2011; 15: 271–276.

    Article  PubMed  Google Scholar 

  20. Bevans M, Mitchell S, Marden S . The symptom experience in the first 100 days following allogeneic hematopoietic stem cell transplantation (HSCT). Support Care Cancer 2008; 16: 1243–1254.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Jim HS, Evans B, Jeong JM, Gonzalez BD, Johnston L, Nelson AM et al. Sleep disruption in hematopoietic cell transplantation recipients: prevalence, severity, and clinical management. Biol Blood Marrow Transplant 2014; 20: 1465–1484.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hacker ED, Kapella MC, Park C, Ferrans CE, Larson JL . Sleep patterns during hospitalization following hematopoietic stem cell transplantation. Oncol Nurs Forum 2015; 42: 371–379.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rischer J, Scherwath A, Zander AR, Koch U, Schulz-Kindermann F . Sleep disturbances and emotional distress in the acute course of hematopoietic stem cell transplantation. Bone Marrow Transplant 2009; 44: 121–128.

    Article  CAS  PubMed  Google Scholar 

  24. Nelson AM, Coe CL, Juckett MB, Rumble ME, Rathouz PJ, Hematti P et al. Sleep quality following hematopoietic stem cell transplantation: longitudinal trajectories and biobehavioral correlates. Bone Marrow Transplant 2014; 49: 1405–1411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Rajkumar SV . Patient information: Multiple myeloma treatment. In: Connor RF, Kyle RA (eds). UpToDate. UpToDate: Waltham, MA, USA, 2016.

    Google Scholar 

  26. Moser NJ, Phillips BA, Guthrie G, Barnett G . Effects of dexamethasone on sleep. Pharmacol Toxicol 1996; 79: 100–102.

    Article  CAS  PubMed  Google Scholar 

  27. Fehm HL, Benkowitsch R, Kern W, Fehm-Wolfsdorf G, Pauschinger P, Born J . Influences of corticosteroids, dexamethasone and hydrocortisone on sleep in humans. Neuropsychobiology 1986; 16: 198–204.

    Article  CAS  PubMed  Google Scholar 

  28. Fortner BV, Stepanski EJ, Wang SC, Kasprowicz S, Durrence HH . Sleep and quality of life in breast cancer patients. J Pain Symptom Manage 2002; 24: 471–480.

    Article  PubMed  Google Scholar 

  29. Delgado-Guay M, Yennurajalingam S, Parsons H, Palmer JL, Bruera E . Association between self-reported sleep disturbance and other symptoms in patients with advanced cancer. J Pain Symptom Manage 2011; 41: 819–827.

    Article  PubMed  Google Scholar 

  30. Mystakidou K, Parpa E, Tsilika E, Gennatas C, Galanos A, Vlahos L . How is sleep quality affected by the psychological and symptom distress of advanced cancer patients? Palliat Med 2009; 23: 46–53.

    Article  CAS  PubMed  Google Scholar 

  31. Fan G, Filipczak L, Chow E . Symptom clusters in cancer patients: a review of the literature. Curr Oncol 2007; 14: 173–179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dodd MJ, Miaskowski C, Lee KA . Occurrence of symptom clusters. J Natl Cancer Inst Monogr 2004; 2004: 76–78.

    Article  Google Scholar 

  33. Donovan KA, Jacobsen PB . Fatigue, depression, and insomnia: evidence for a symptom cluster in cancer. Semin Oncol Nurs 2007; 23: 127–135.

    Article  PubMed  Google Scholar 

  34. Theobald DE . Cancer pain, fatigue, distress, and insomnia in cancer patients. Clin Cornerstone 2004; 6: S15–S21.

    Article  PubMed  Google Scholar 

  35. Roscoe JA, Kaufman ME, Matteson-Rusby SE, Palesh OG, Ryan JL, Kohli S et al. Cancer-related fatigue and sleep disorders. Oncologist 2007; 12: 35–42.

    Article  PubMed  Google Scholar 

  36. Ancoli-Israel S, Moore PJ, Jones V . The relationship between fatigue and sleep in cancer patients: a review. Eur J Cancer Care (Engl) 2001; 10: 245–255.

    Article  CAS  Google Scholar 

  37. Chao N . Clinical manifestations, diagnosis, and grading of chronic graft-versus-host disease. In: Negrin RS, Connor RF(eds). UpToDate. UpToDate: Waltham, MA, USA, 2016.

    Google Scholar 

  38. Becker H, Stuifbergen A, Morrison J . Promising new approaches to assess cognitive functioning in people with multiple sclerosis. Int J MS Care 2012; 14: 71–76.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Becker H, Stuifbergen A, Lee H, Kullberg V . Reliability and validity of PROMIS cognitive abilities and cognitive concerns scales among people with multiple sclerosis. Int J MS Care 2014; 16: 1–8.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Stewart AL, Ware JE, Brook RH, Davies AR . Conceptualization and measurement of health for adults in the Health Insurance Study. Vol II. Physical health in terms of functioning. The RAND Corporation: Santa Monica, CA, USA, 1978.

    Google Scholar 

  41. Hays RD, Stewart AL . Sleep measures In: Stewart AL, Ware JE (eds). Measuring Functioning and Well-being: The Medical Outcomes Study Approach. Duke University Press: Durham, NC, USA, 1992, pp 235–259.

    Google Scholar 

  42. Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR . Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J Clin Oncol 2000; 18: 743.

    Article  CAS  PubMed  Google Scholar 

  43. Smith MT, Wegener ST . Measures of sleep: The Insomnia Severity Index, Medical Outcomes Study (MOS) Sleep Scale, Pittsburgh Sleep Diary (PSD), and Pittsburgh Sleep Quality Index (PSQI). Arthritis Care Res 2003; 49: S184–S196.

    Article  Google Scholar 

  44. Allen RP, Kosinski M, Hill-Zabala CE, Calloway MO . Psychometric evaluation and tests of validity of the Medical Outcomes Study 12-item Sleep Scale (MOS sleep). Sleep Med 2009; 10: 531–539.

    Article  PubMed  Google Scholar 

  45. Hays RD, Martin SA, Sesti AM, Spritzer KL . Psychometric properties of the medical outcomes study sleep measure. Sleep Med 2005; 6: 41–44.

    Article  PubMed  Google Scholar 

  46. Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S et al. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol 2010; 63: 1179–1194.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Junghaenel DU, Schneider S, Stone AA, Christodoulou C, Broderick JE . Ecological validity and clinical utility of Patient-Reported Outcomes Measurement Information System (PROMIS(R)) instruments for detecting premenstrual symptoms of depression, anger, and fatigue. J Psychosom Res 2014; 76: 300–306.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Broderick JE, Schneider S, Junghaenel DU, Schwartz JE, Stone AA . Validity and reliability of patient-reported outcomes measurement information system instruments in osteoarthritis. Arthritis Care Res 2013; 65: 1625–1633.

    Google Scholar 

  49. Bartlett SJ, Orbai A-M, Duncan T, DeLeon E, Ruffing V, Clegg-Smith K et al. Reliability and validity of selected PROMIS measures in people with rheumatoid arthritis. PLoS ONE 2015; 10: e0138543.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Cleeland CS (ed). Measurement of Pain by Subjective Report. Raven Press: New York, USA, 1989.

    Google Scholar 

  51. Serlin RC, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS . When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain 1995; 61: 277–284.

    Article  CAS  PubMed  Google Scholar 

  52. IBM Corp. Released 2010. IBM SPSS Statistics for Windows, Version 19.0. IBM Corp: Armonk, NY, USA, 2010.

  53. Negrin RS . Preparative regimens for hematopoietic cell transplantation. In: Chao N, Connor RF (eds). UpToDate, vol. Topic 3557. UpToDate: Waltham, MA, USA, 2014.

    Google Scholar 

  54. Garland SN, Johnson JA, Savard J, Gehrman P, Perlis M, Carlson L et al. Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. Neuropsychiatr Dis Treat 2014; 10: 1113–1124.

    PubMed  PubMed Central  Google Scholar 

  55. Todd BL, Feuerstein EL, Feuerstein M . When breast cancer survivors report cognitive problems at work. Int J Psychiatry Med 2011; 42: 279–294.

    Article  PubMed  Google Scholar 

  56. Jacobs SR, Jacobsen PB, Booth-Jones M, Wagner LI, Anasetti C . Evaluation of the functional assessment of cancer therapy cognitive scale with hematopoetic stem cell transplant patients. J Pain Symptom Manage 2007; 33: 13–23.

    Article  PubMed  Google Scholar 

  57. Association AP Diagnostic and Statistical Manual of Mental Disorders: DSM-5. American Psychiatric Association: Washington, D.C., 2013.

  58. Bower JE . Cancer-related fatigue—mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 2014; 11: 597–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gielissen MF, Schattenberg AV, Verhagen CA, Rinkes MJ, Bremmers ME, Bleijenberg G . Experience of severe fatigue in long-term survivors of stem cell transplantation. Bone Marrow Transplant 2007; 39: 595–603.

    Article  CAS  PubMed  Google Scholar 

  60. Lee SJ, Joffe S, Kim HT, Socie G, Gilman AL, Wingard JR et al. Physicians' attitudes about quality-of-life issues in hematopoietic stem cell transplantation. Blood 2004; 104: 2194–2200.

    Article  CAS  PubMed  Google Scholar 

  61. Madsen MT, Huang C, Gögenur I . Actigraphy for measurements of sleep in relation to oncological treatment of patients with cancer: a systematic review. Sleep Med Rev 2015; 20: 73–83.

    Article  PubMed  Google Scholar 

  62. Faiz SA, Balachandran D, Hessel AC, Lei X, Beadle BM, William WN Jr. et al. Sleep-related breathing disorders in patients with tumors in the head and neck region. Oncologist 2014; 19: 1200–1206.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Zhou J, Jolly S . Obstructive sleep apnea and fatigue in head and neck cancer patients. Am J Clin Oncol 2015; 38: 411–414.

    Article  PubMed  Google Scholar 

  64. Banno K, Kryger MH . Sleep apnea: clinical investigations in humans. Sleep Med 2007; 8: 400–426.

    Article  PubMed  Google Scholar 

  65. Fleming L, Randell K, Harvey CJ, Espie CA . Does cognitive behaviour therapy for insomnia reduce clinical levels of fatigue, anxiety and depression in cancer patients? Psycho-oncology 2014; 23: 679–684.

    Article  PubMed  Google Scholar 

  66. Savard J, Simard S, Ivers H, Morin CM . Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: sleep and psychological effects. J Clin Oncol 2005; 23: 6083–6096.

    Article  PubMed  Google Scholar 

  67. Espie CA, Fleming L, Cassidy J, Samuel L, Taylor LM, White CA et al. Randomized controlled clinical effectiveness trial of cognitive behavior therapy compared with treatment as usual for persistent insomnia in patients with cancer. J Clin Oncol 2008; 26: 4651–4658.

    Article  PubMed  Google Scholar 

  68. Perlis ML, Jungquist C, Smith MT, Posner D . Cognitive Behavioral Treatment of Insomnia: A Session-by-Session Guide. Springer: New York, 2005.

    Google Scholar 

  69. Young JS, Bourgeois JA, Hilty DM, Hardin KA . Sleep in hospitalized medical patients, part 2: behavioral and pharmacological management of sleep disturbances. J Hosp Med 2009; 4: 50–59.

    Article  PubMed  Google Scholar 

  70. Mustian KM, Sprod LK, Janelsins M, Peppone LJ, Mohile S . Exercise recommendations for cancer-related fatigue, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfunction: a review. Oncol Hematol Rev 2012; 8: 81–88.

    PubMed  PubMed Central  Google Scholar 

  71. Baumann FT, Zopf EM, Nykamp E, Kraut L, Schüle K, Elter T et al. Physical activity for patients undergoing an allogeneic hematopoietic stem cell transplantation: benefits of a moderate exercise intervention. Eur J Haematol 2011; 87: 148–156.

    Article  PubMed  Google Scholar 

  72. Wiskemann J, Dreger P, Schwerdtfeger R, Bondong A, Huber G, Kleindienst N et al. Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation. Blood 2011; 117: 2604–2613.

    Article  CAS  PubMed  Google Scholar 

  73. Jarden M, Nelausen K, Hovgaard D, Boesen E, Adamsen L . The effect of a multimodal intervention on treatment-related symptoms in patients undergoing hematopoietic stem cell transplantation: a randomized controlled trial. J Pain Symptom Manage 2009; 38: 174–190.

    Article  PubMed  Google Scholar 

  74. Harder H, Van Gool AR, Cornelissen JJ, Duivenvoorden HJ, Eijkenboom WMH, Barge RMY et al. Assessment of pre-treatment cognitive performance in adult bone marrow or haematopoietic stem cell transplantation patients: a comparative study. Eur J Cancer 2005; 41: 1007–1016.

    Article  PubMed  Google Scholar 

  75. Saykin AJ, Wishart HA, Rabin LA, Santulli RB, Flashman LA, West JD et al. Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology 2006; 67: 834–842.

    Article  CAS  PubMed  Google Scholar 

  76. Moul DE, Hall M, Pilkonis PA, Buysse DJ . Self-report measures of insomnia in adults: rationales, choices, and needs. Sleep Med Rev 2004; 8: 177–198.

    Article  PubMed  Google Scholar 

  77. Rollig C, Knop S, Bornhauser M . Multiple myeloma. Lancet 2015; 385: 2197–2208.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

NIH K07CA138767, Internal Funding from Duke Cancer Patient Support.

Author information

Authors and Affiliations

  1. Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

    S E Ghazikhanian, C S Dorfman, T J Somers, M L O'Sullivan, S A Kelleher, K A Rowe Nichols, N Chao & R A Shelby

  2. Department of Psychology, University of Miami, Coral Gables, FL, USA

    H M Fisher

  3. Health Psychology, VA Connecticut Healthcare System, New Haven, CT, USA

    S N Edmond

  4. Department of Anesthesiology, Perioperative and Pain Medicine, Standford University Medical Center, Palo Alto, CA, USA

    A A Wren

Authors
  1. S E Ghazikhanian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C S Dorfman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T J Somers
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M L O'Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H M Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S N Edmond
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A A Wren
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S A Kelleher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K A Rowe Nichols
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. N Chao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R A Shelby
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R A Shelby.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghazikhanian, S., Dorfman, C., Somers, T. et al. Cognitive problems following hematopoietic stem cell transplant: relationships with sleep, depression and fatigue. Bone Marrow Transplant 52, 279–284 (2017). https://doi.org/10.1038/bmt.2016.248

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.248

This article is cited by

Search

Advanced search

Quick links