Skip to main content
Log in

Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence

  • Chronic Pain (R Staud, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Cognitive difficulties represent a common and debilitating feature of the enigmatic chronic fatigue syndrome (CFS). These difficulties manifest as self-reported problems with attention, memory, and concentration and present objectively as slowed information processing speed particularly on complex tasks requiring sustained attention. The mechanisms underlying cognitive dysfunction remain to be established; however, alterations in autonomic nervous system activity and cerebral blood flow have been proposed as possibilities. Heterogeneity in the experience of cognitive impairment, as well as differences in the methods utilised to quantify dysfunction, may contribute to the difficulties in establishing plausible biological underpinnings. The development of a brief neurocognitive battery specifically tailored to CFS and adoption by the international research community would be beneficial in establishing a profile of cognitive dysfunction. This could also provide better insights into the underlying biological mechanisms of cognitive dysfunction in CFS and enhance the development of targeted treatments.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994;121:953–9.

    Article  CAS  PubMed  Google Scholar 

  2. White PD, Chalder T, Sharpe M. The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial. BJPsych Bulletin. 2015;39(1):24–7. doi:10.1192/pb.bp.113.045005.

    Article  PubMed  PubMed Central  Google Scholar 

  3. White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M, PACE Trial Management Group. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med. 2013;43(10):2227–35. doi:10.1017/S0033291713000020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011;377(9768):823–36. doi:10.1016/S0140-6736(11)60096-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Castell BD, Kazantzis N, Moss-Morris RE. Cognitive behavioral therapy and graded exercise for chronic fatigue syndrome: a meta-analysis. Clin Psych Sci Pract. 2011;18(4):311–24. doi:10.1111/j.1468-2850.2011.01262.x.

    Article  Google Scholar 

  6. Lloyd AR, van der Meer JWM. The long wait for a breakthrough in chronic fatigue syndrome. BMJ. 2015;350. doi:10.1136/bmj.h2087.

  7. Aslakson E, Vollmer-Conna U, Reeves WC, White PD. Replication of an empirical approach to delineate the heterogeneity of chronic unexplained fatigue. Popul Health Met. 2009;7(17):1–10. doi:10.1186/1478-7954-7-17.

    Google Scholar 

  8. Aslakson E, Vollmer-Conna U, White PD. The validity of an empirical delineation of heterogeneity in chronic unexplained fatigue. Pharmacogenomics. 2006;7(3):365–73. doi:10.2217/14622416.7.3.365.

    Article  PubMed  Google Scholar 

  9. Cella M, Chalder T, White PD. Does the heterogeneity of chronic fatigue syndrome moderate the response to cognitive behaviour therapy? An exploratory study. Psychother Psychosom. 2011;80(6):353–8.

    Article  PubMed  Google Scholar 

  10. Vollmer-Conna U, Aslakson E, White PD. An empirical delineation of the heterogeneity of chronic unexplained fatigue in women. Pharmacogenomics. 2006;7(3):355–64. doi:10.2217/14622416.7.3.355.

    Article  PubMed  Google Scholar 

  11. Wilson A, Hickie I, Hadzi-Pavlovic D, Wakefield D, Parker G, Straus SE, et al. What is chronic fatigue syndrome? Heterogeneity within an international multicentre study. Aust N Z J Psychiatry. 2001;35(4):520–7. doi:10.1046/j.1440-1614.2001.00888.x.

    Article  CAS  PubMed  Google Scholar 

  12. Komaroff A. Clinical presentation of chronic fatigue syndrome. In: Bock GWJ, editor. Chronic fatigue syndrome. Hoboken, New Jersey: Ciba Foundation Symposium; 1993. p. 43–61.

    Google Scholar 

  13. Ocon AJ. Caught in the thickness of brain fog: exploring the cognitive symptoms of chronic fatigue syndrome. Frontiers in Physiology. 2013;4. doi:10.3389/fphys.2013.00063.

  14. Holgate ST, Komaroff AL, Mangan D, Wessely S. Chronic fatigue syndrome: understanding a complex illness. Nat Rev Neurosci. 2011;12(9):539–44.

    Article  CAS  PubMed  Google Scholar 

  15. Christodoulou C, DeLuca J, Lange G, Johnson SK, Sisto SA, Korn L, et al. Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998;64(4):431–4. doi:10.1136/jnnp.64.4.431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, et al. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999;159(18):2129–37. doi:10.1001/archinte.159.18.2129.

    Article  CAS  PubMed  Google Scholar 

  17. Jason LA, Shanks LL, Evans M, Brown A. Cognitive impairments associated with CFS and POTS. Frontiers in Physiology. 2013;4. doi:10.3389/fphys.2013.00113.

  18. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Arthritis Rheum. 1990;33(2):160–72. doi:10.1002/art.1780330203.

    Article  CAS  PubMed  Google Scholar 

  19. Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011;270(4):327–38. doi:10.1111/j.1365-2796.2011.02428.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cockshell SJ, Mathias JL. Cognitive functioning in chronic fatigue syndrome: a meta-analysis. Psychol Med. 2010;40:1253–67. doi:10.1017/S0033291709992054.

    Article  CAS  PubMed  Google Scholar 

  21. Michiels V, Clydts R. Neuropsychological functioning in chronic fatigue syndrome: a review. Acta Psychiatr Scand. 2001;103(2):84–93. doi:10.1034/j.1600-0447.2001.00017.x.

    Article  CAS  PubMed  Google Scholar 

  22. Christley Y, Duffy T, Everall I, Martin C. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013;15(4):1–9. doi:10.1007/s11920-013-0353-8.

    Article  Google Scholar 

  23. Glass JM. Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions. Curr Rheumatol Rep. 2006;8(6):425–9. doi:10.1007/s11926-006-0036-0.

    Article  PubMed  Google Scholar 

  24. Moss-Morris R, Petrie KJ, Large RG, Kydd RR. Neuropsychological deficits in chronic fatigue syndrome: artifact or reality? J Neurol Neurosurg Psychiatr. 1996;60(5):474–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, et al. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2003;3(1):1–9. doi:10.1186/1472-6963-3-25.

    Article  Google Scholar 

  26. Cockshell SJ, Mathias JL. Cognitive deficits in chronic fatigue syndrome and their relationship to psychological status, symptomatology, and everyday functioning. Neuropsychology. 2013;27(2):230–42. doi:10.1037/a0032084.

    Article  PubMed  Google Scholar 

  27. Cockshell SJ, Mathias JL. Cognitive functioning in people with chronic fatigue syndrome: a comparison between subjective and objective measures. Neuropsychology. 2014;28(3):394–405. doi:10.1037/neu0000025. This study provides convincing evidence of a disconnect between subjective perceptions and objective cognitive performance, that is not specific to individuals with chronic fatigue syndrome.

    Article  PubMed  Google Scholar 

  28. Nakatomi Y, Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, et al. Neuroinflammation in patients with chronic fatigue syndrome/myalgic encephalomyelitis: an 11C-(R)-PK11195 PET study. J Nucl Med. 2014;55(6):945–50. doi:10.2967/jnumed.113.131045. Provide preliminary evidence of an association between positron emission tomography-derived neuroinflammation and self-reported cognitive difficulties in chronic fatigue syndrome.

    Article  CAS  PubMed  Google Scholar 

  29. Schmaling K, Betterton K. Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia. Qual Life Res. 2015:1–7. doi:10.1007/s11136-015-1160-y.

  30. Ickmans K, Meeus M, Kos D, Clarys P, Meersdom G, Lambrecht L, et al. Cognitive performance is of clinical importance, but is unrelated to pain severity in women with chronic fatigue syndrome. Clin Rheumatol. 2013;32(10):1475–85. doi:10.1007/s10067-013-2308-1.

    Article  PubMed  Google Scholar 

  31. Meeus M, Ickmans K, Struyf F, Kos D, Lambrecht L, Willekens B, et al. What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia. Clin Rheumatol. 2014:1–13. doi:10.1007/s10067-014-2793-x.

  32. Gotts ZM, Ellis JG, Deary V, Barclay N, Newton JL. The association between daytime napping and cognitive functioning in chronic fatigue syndrome. PLoS One. 2015;10(1), e0117136. doi:10.1371/journal.pone.0117136.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Attree EA, Arroll MA, Dancey CP, Griffith C, Bansal AS. Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome. Psychol Res Behav Manag. 2014;7:67–76. doi:10.2147/prbm.s50645.

    PubMed  PubMed Central  Google Scholar 

  34. Ickmans K, Clarys P, Nijs J, Meeus M, Aerenhouts D, Zinzen E, et al. Association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome. J Rehabil Res Dev. 2013;50(6):795–810. doi:10.1682/JRRD.2012.08.0156.

    Article  PubMed  Google Scholar 

  35. Ickmans K, Meeus M, De Kooning M, Lambrecht L, Pattyn N, Nijs J. Can recovery of peripheral muscle function predict cognitive task performance in chronic fatigue syndrome with and without fibromyalgia? Phys Ther. 2014;94(4):511–22. doi:10.2522/ptj.20130367.

    Article  PubMed  Google Scholar 

  36. Ickmans K, Meeus M, De Kooning M, Lambrecht LJ, Pattyn N, Nijs J. Associations between cognitive performance and pain in chronic fatigue syndrome: comorbidity with fibromyalgia does matter. Pain Physician. 2015;18(5):E841–E52.

    PubMed  Google Scholar 

  37. Togo F, Lange G, Natelson BH, Quigley KS. Attention network test: assessment of cognitive function in chronic fatigue syndrome. J Neuropsychol. 2015;9(1):1–9. doi:10.1111/jnp.12030.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Neu D, Mairesse O, Montana X, Gilson M, Corazza F, Lefevre N, et al. Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome. Eur J Appl Physiol. 2014;114(9):1841–51. doi:10.1007/s00421-014-2910-1.

    Article  CAS  PubMed  Google Scholar 

  39. Beaumont A, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U. Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. PLoS One. 2012;7(11):e49518. doi:10.1371/journal.pone.0049518. First study to demonstrate an association between resting heart variability and objective measures of cognitive performance in participants with chronic fatigue syndrome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol. 1935;18:643–62.

    Article  Google Scholar 

  41. Fan J, McCandliss BD, Sommer T, Raz A, Posner MI. Testing the efficiency and independence of attentional networks. J Cogn Neurosci. 2002;14(3):340–7. doi:10.1162/089892902317361886.

    Article  PubMed  Google Scholar 

  42. Hou R, Moss-Morris R, Risdale A, Lynch J, Jeevaratnam P, Bradley BP, et al. Attention processes in chronic fatigue syndrome: attentional bias for health-related threat and the role of attentional control. Behav Res Ther. 2014;52:9–16. doi:10.1016/j.brat.2013.10.005.

    Article  PubMed  Google Scholar 

  43. Cook DB, O’Connor PJ, Lange G, Steffener J. Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. Neuroimage. 2007;36(1):108–22. doi:10.1016/j.neuroimage.2007.02.033.

    Article  PubMed  Google Scholar 

  44. Lange G, Steffener J, Cook DB, Bly BM, Christodoulou C, Liu WC, et al. Objective evidence of cognitive complaints in chronic fatigue syndrome: a BOLD fMRI study of verbal working memory. Neuroimage. 2005;26(2):513–24. doi:10.1016/j.neuroimage.2005.02.011.

    Article  CAS  PubMed  Google Scholar 

  45. Caseras X, Mataix-Cols D, Giampietro V, Rimes KA, Brammer M, Zelaya F, et al. Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task. Psychosom Med. 2006;68(6):947–55. doi:10.1097/01.psy.0000242770.50979.5f.

    Article  PubMed  Google Scholar 

  46. Boissoneault J, Letzen J, Lai S, O’Shea A, Craggs J, Robinson M, et al. Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study. Magn Reson Imaging. in press. doi:10.1016/j.mri.2015.12.008. Utilise novel neuroimaging techniques to explore abnormalities in resting state functional connectivity in chronic fatigue syndrome.

  47. Mizuno K, Tanaka M, Tanabe HC, Joudoi T, Kawatani J, Shigihara Y, et al. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome. NeuroImage Clinical. 2015;9:355–68. doi:10.1016/j.nicl.2015.09.001.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Arroll MA, Attree EA, O’Leary JM, Dancey CP. The delayed fatigue effect in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Fatigue: Biomedicine, Health & Behavior. 2014;2(2):57–63. doi:10.1080/21641846.2014.892755.

    Google Scholar 

  49. Keech A, Sandler CX, Vollmer-Conna U, Cvejic E, Lloyd AR, Barry BK. Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome. J Psychosom Res. 2015;79(6):537–49. doi:10.1016/j.jpsychores.2015.08.008.

    Article  PubMed  Google Scholar 

  50. Yamamoto S, Ouchi Y, Nakatsuka D, Tahara T, Mizuno K, Tajima S, et al. Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor. PLoS One. 2012;7(12), e51515. doi:10.1371/journal.pone.0051515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cockshell SJ, Mathias JL. Test effort in persons with chronic fatigue syndrome when assessed using the validity indicator profile. J Clin Exp Neuropsychol. 2012;34(7):679–87. doi:10.1080/13803395.2012.668176. Provide good evidence that poor test effort unlikely accounts for the neurocognitive dysfunction in chronic fatigue syndrome.

    Article  PubMed  Google Scholar 

  52. Santamarina-Perez P, Eiroa-Orosa FJ, Rodriguez-Urrutia A, Qureshi A, Alegre J. Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study. Applied Neuropsychology: Adult. 2013:1–8. doi:10.1080/09084282.2013.771264.

  53. Van Cauwenbergh D, Nijs J, Kos D, Van Weijnen L, Struyf F, Meeus M. Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review. Eur J Clin Invest. 2014;44(5):516–26. doi:10.1111/eci.12256.

    Article  PubMed  Google Scholar 

  54. Meeus M, Goubert D, De Backer F, Struyf F, Hermans L, Coppieters I, et al. Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. Semin Arthritis Rheum. 2013;43(2):279–87. doi:10.1016/j.semarthrit.2013.03.004.

    Article  PubMed  Google Scholar 

  55. Stewart JM, Medow MS, Messer ZR, Baugham IL, Terilli C, Ocon AJ. Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome. Am J Physiol Heart Circ Physiol. 2012;302(5):H1185–H94. doi:10.1152/ajpheart.00994.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ocon AJ, Messer ZR, Medow MS, Stewart JM. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome. Clin Sci. 2012;122(5):227–38. doi:10.1042/cs20110241.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Medow MS, Sood S, Messer Z, Dzogbeta S, Terilli C, Stewart JM. Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome. J Appl Physiol. 2014;117(10):1157–64. doi:10.1152/japplphysiol.00527.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Larun L, Brurbeg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews. 2015;Issue 2:Art. No.:CD003200. doi:10.1002/14651858.CD003200.pub3.

  59. Wearden A, Appleby L. Cognitive performance and complaints of cognitive impairment in chronic fatigue syndrome (CFS). Psychol Med. 1997;27(1):81–90. doi:10.1017/S0033291796004035.

    Article  CAS  PubMed  Google Scholar 

  60. Vollmer-Conna U, Wakefield D, Lloyd A, Hickie I, Lemon J, Bird KD, et al. Cognitive deficits in patients suffering from chronic fatigue syndrome, acute infective illness or depression. Br J Psychiatry. 1997;171:377–81. doi:10.1192/bjp.171.4.377.

    Article  CAS  PubMed  Google Scholar 

  61. Ray C, Phillips L, Weir WRC. Quality of attention in chronic fatigue syndrome: subjective reports of everyday attention and cognitive difficulty, and performance on tasks of focused attention. Br J Clin Psychol. 1993;32(3):357–64. doi:10.1111/j.2044-8260.1993.tb01068.x.

    Article  PubMed  Google Scholar 

  62. Goedendorp MM, van der Werf SP, Bleijenberg G, Tummers M, Knoop H. Does neuropsychological test performance predict outcome of cognitive behavior therapy for chronic fatigue syndrome and what is the role of underperformance? J Psychosom Res. 2013;75(3):242–8. doi:10.1016/j.jpsychores.2013.07.011.

    Article  PubMed  Google Scholar 

  63. Twisk FNM. Underperformance of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) patients at neurocognitive tests should be assessed objectively without an a priori judgment about the etiology. J Psychosom Res. 2014;76(4):339. doi:10.1016/j.jpsychores.2013.10.016.

    Article  PubMed  Google Scholar 

  64. Young JL. Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study. Psychiatry Res. 2013;207(1–2):127–33. doi:10.1016/j.psychres.2012.09.007.

    Article  CAS  PubMed  Google Scholar 

  65. Maroti D, Westerberg AF, Saury J-M, Bileviciute-Ljungar I. Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study. J Rehabil Med. 2015;47(7):665–8. doi:10.2340/16501977-1976.

    PubMed  Google Scholar 

  66. Adamowicz J, Caikauskaite I, Friedberg F. Defining recovery in chronic fatigue syndrome: a critical review. Qual Life Res. 2014;23(9):2407–16. doi:10.1007/s11136-014-0705-9.

    Article  PubMed  Google Scholar 

  67. DiPino RK, Kane RL. Neurocognitive functioning in chronic fatigue syndrome. Neuropsychol Rev. 1996;6(1):47–60. doi:10.1007/bf01875419.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Uté Vollmer-Conna.

Ethics declarations

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This is part of the Topical Collection on Chronic Pain

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cvejic, E., Birch, R.C. & Vollmer-Conna, U. Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence. Curr Rheumatol Rep 18, 24 (2016). https://doi.org/10.1007/s11926-016-0577-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-016-0577-9

Keywords

Navigation