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Year : 2014  |  Volume : 7  |  Issue : 4  |  Page : 422-424  

Cognitive impairments in chronic fatigue syndrome

Department of Psychiatry, Pravara Institute of Medical Sciences (Deemed University), Rural Medical College, Loni, Maharashtra, India

Date of Web Publication25-Jun-2014

Correspondence Address:
Suprakash Chaudhury
Department of Psychiatry, Pravara Institute of Medical Sciences (Deemed University), Rural Medical College, Loni, Maharashtra
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
Chaudhury S. Cognitive impairments in chronic fatigue syndrome. Med J DY Patil Univ 2014;7:422-4

How to cite this URL:
Chaudhury S. Cognitive impairments in chronic fatigue syndrome. Med J DY Patil Univ [serial online] 2014 [cited 2022 Sep 25];7:422-4. Available from:

Chronic fatigue syndrome (CFS) is a severe, chronic and disabling disease characterized by intense fatigue in addition to cognitive, autonomic, neuroendocrine, immunoallergic and musculoskeletal symptoms, which are of recent appearance and that cannot be explained by other clinical conditions, lasting for at least 6 months, is not alleviated by rest and which worsens with physical or mental activity, with very slow recovery and a reduction of >50% of activities of daily living previously performed by the patient. In spite of it being recognized as a disease by the WHO since 1989 (classified as G93.3 in the ICD-10), CFS is still largely unknown by most health professionals. [1]

Despite the heterogeneity of symptoms of CFS, up to 85-95% of individuals experience cognitive impairments (CI) such as slow thinking, difficulty focusing, confusion, lack of concentration, forgetfulness, or haziness in thought processes, which have subjectively been described by patients as "brain fog." CI in CFS involve problems with visual memory, verbal memory, short-term and long-term recall, attention span, reaction times, concentration, and complex information processing. [2],[3] The CI in CFS is localized to the domains of attention, information processing, memory and reaction time on neurocognitive testing. [4] These CI may adversely affect daily functioning. Memory deficits could lead to impairments in daily functioning as well as difficulties in school and at work. Students with CFS could have difficulty with tasks such as remembering information presented in a lecture, whereas adults with CFS could have difficulty at work with remembering tasks assigned to them. [3]

One potential explanation for cognitive deficits in patients with CFS is a concept known as kindling, a type of central nervous system (CNS) impairment. Kindling theory states that when neurons are repeatedly exposed to a stimulus, they can eventually reach a point of hypersensitivity. This state of hypersensitivity can induce seizure like activity. In other words, patients with CFS might be exposed to repeated low-intensity stimulation brought on by a virus. The seizures ultimately induced by such stimulation could spread to the rest of the brain and become the root of a number of CFS symptoms. [5] Another theory potentially explaining cognitive difficulties among patients with CFS focuses a significant decline in gray matter (GM) volume among those with CFS when compared with the healthy controls. This marked reduction in GM could explain the fatigue and cognitive deficits associated with CFS. A non-pharmacological intervention provided to patients with CFS led to significant increases in GM, localized in the lateral prefrontal cortex. This change in GM was also related to significant improvements in cognitive speed among patients with CFS, and provides evidence supporting the relationship between the CNS and CI in patients with CFS. [3],[6]

Magnetic resonance imaging studies report increased hyperintensities in the frontal lobe subcortical white matter of CFS subjects without psychiatric comorbidities compared to those with comorbidities and control subjects, suggesting nonspecific cerebral lesions as the basis for CI. [7] Using functional magnetic resonance imaging to measure cerebral changes during cognitive tasks, it was found that CFS subjects exhibited decreased caudate nucleus activity, increased recruitment of cerebral regions and an inactive ventral anterior cingulate cortex during the errors compared with the control subjects. These changes may be associated with fatigue, the need for additional neural activation to complete a task, and reduced motivation. [8] Advanced imaging techniques of Xenon gas diffusion computed tomography [9] and magnetic resonance arterial spin labeling [10] have demonstrated reduced total cerebal blood flow in CFS subjects compared with the controls. The chronic cerebral hypoperfusion may result in CI. [2]

Impaired functioning of the norepinephrine transporter (NET) contributes to orthostatic intolerance (OI), a symptom of CFS. [11] OI occurs when patients with CFS stand up quickly and become dizzy and lightheaded. If OI occurs when the NET is inhibited, then impairments with the NET could help explain the CI and mental cloudiness associated among patients with CFS. Abnormalities of central neurotransmitters including corticotrophin-releasing hormone (CRH) has also been reported. The main function of CRH is to produce behavioral and locomotors function. Deficiency of CRH could explain chronic fatigue and the associated CI in CFS. [3] A recent study found that in female patients with CFS, lower peak oxygen uptake and peak heart rate were associated with slower psychomotor speed. Maximal handgrip strength was correlated with working memory performance. Both choice and simple reaction time were lower in patients with CFS relative to healthy controls. The authors conclude that physical fitness is associated with cognitive performance in CFS. [12]

A large follow-up (n = 834; 8-20 months) of CFS patients attending specialist CFS services revealed significant improvement in fatigue, physical function, anxiety, depression and pain. Worse fatigue, physical function and pain at clinical assessment predicted a worse outcome for fatigue at follow-up. [13] Until date, treatment of CFS have focused on improving the physical fatigued state rather than the CI. Meta-analyses demonstrate that cognitive behavioral therapy and graded exercise therapy effectively treat CFS in many individuals. [14] It is possible that cognitive symptoms may also improve with such therapies. Future studies should focus on this aspect of CFS.

  References Top

1.Qanneta R, Fontova R, Poveda MJ, Castro S. Clinical typology of chronic fatigue syndrome: Classificatory hypothesis. Reumatol Clin 2014;10:132-3.  Back to cited text no. 1
2.Ocon AJ. Caught in the thickness of brain fog: Exploring the cognitive symptoms of chronic fatigue syndrome. Front Physiol 2013;4:63.  Back to cited text no. 2
3.Shanks L, Jason LA, Evans M, Brown A. Cognitive impairments associated with CFS and POTS. Front Physiol 2013;4:113.  Back to cited text no. 3
4.Cockshell SJ, Mathias JL. Cognitive functioning in chronic fatigue syndrome: A meta-analysis. Psychol Med 2010;40:1253-67.  Back to cited text no. 4
5.Jason LA, Sorenson M, Porter N, Belkairous N. An etiological model for myalgic encephalomyelitis/chronic fatigue syndrome. Neurosci Med 2011;2:14-27.  Back to cited text no. 5 Lange FP, Koers A, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, et al. Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. Brain 2008;131:2172-80.  Back to cited text no. 6
7.Lange G, DeLuca J, Maldjian JA, Lee H, Tiersky LA, Natelson BH. Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci 1999;171:3-7.  Back to cited text no. 7
8.De Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, van der Meer JW, et al. Neural correlates of the chronic fatigue syndrome - An fMRI study. Brain 2004;127:1948-57.  Back to cited text no. 8
9.Yoshiuchi K, Farkas J, Natelson BH. Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging 2006;26:83-6.  Back to cited text no. 9
10.Biswal B, Kunwar P, Natelson BH. Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling. J Neurol Sci 2011;301:9-11.  Back to cited text no. 10
11.Bayles R, Harikrishnan KN, Lambert E, Baker EK, Agrotis A, Guo L, et al. Epigenetic modification of the norepinephrine transporter gene in postural tachycardia syndrome. Arterioscler Thromb Vasc Biol 2012;32:1910-6.  Back to cited text no. 11
12.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;50:795-810.  Back to cited text no. 12
13.Crawley E, Collin SM, White PD, Rimes K, Sterne JA, May MT, et al. Treatment outcome in adults with chronic fatigue syndrome: A prospective study in England based on the CFS/ME National Outcomes Database. QJM 2013;106:555-65.  Back to cited text no. 13
14.Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behavior therapy for chronic fatigue syndrome in adults. Cochrane Database Syst Rev 2008:CD001027.  Back to cited text no. 14


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