ME and CFS Medical Abnormalities – Cognitive Impairment

 

Following is a list of articles about abnormalities in cognition in ME and CFS.

Links to the more than 1,000 peer-reviewed journal articles are listed on the M.E. and CFS Medical Abnormalities page of this website.

 

Mizuno K, Tanaka M, Tanabe HC, Joudoi T, Kawatani J, Shigihara Y, Tomoda A, Miike T, Imai-Matsumura K, Sadato N,Watanabe Y. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome. Neuroimage Clin. 2015 Sep 10;9:355-68. PMID: 26594619

The authors conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients with childhood CFS exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension.

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Nijhof LN, Nijhof SL, Bleijenberg G, Stellato RK, Kimpen JL, Hulshoff Pol HE, van de Putte EM. The impact of chronic fatigue syndrome on cognitive functioning in adolescents. Eur J Pediatr. 2016 Feb;175(2):245-52. PMID: 26334394

Current IQ scores of CFS adolescents were lower than expected on the basis of their school level. Furthermore, there was a difference in intelligence performance across time when current IQ scores were compared with pre-CFS cognitive achievement.

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Sulheim D, Fagermoen E, Sivertsen ØS, Winger A, Wyller VB, Øie MG. Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study. Arch Dis Child. 2015 Sep;100(9):838-44. PMID: 25791841

Adolescents with chronic fatigue had impaired cognitive function of clinical relevance, measured by objective cognitive tests, in comparison to HC. Working memory and processing speed may represent core difficulties.

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Cockshell SJ, Mathias JL. Cognitive deficits in chronic fatigue syndrome and their relationship to psychological status, symptomatology, and everyday functioning. Neuropsychology. 2013 Mar;27(2):230-42. PMID: 23527651

Compared to controls, a group of CFS patients showed impaired information processing speed (reaction time) but comparable performance on tests of attention, memory, motor functioning, verbal ability, and visuospatial ability. Moreover, information processing speed was not related to psychiatric status, depression, anxiety, the number or severity of CFS symptoms, fatigue, sleep quality, or everyday functioning.

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Togo F, Lange G, Natelson BH, Quigley KS. Attention network test: Assessment of cognitive function in chronic fatigue syndrome. J Neuropsychol. 2013 Sep 24. PMID: 24112872

Comparison of data from two groups of CFS patients (those with and without comorbid major depressive disorder) to controls consistently showed that error rates did not differ among groups across conditions, but speed of information processing did. Processing time was prolonged in both CFS groups and most significantly affected in response to the most complex task conditions. For simpler tasks, processing time was only prolonged in CFS participants with depression.

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Hutchinson CV, Badham SP. Patterns of Abnormal Visual Attention in Myalgic Encephalomyelitis. Optom Vis Sci. 2013 May 17. PMID: 23689679

In a study of visual attention difficulties, CFS patients exhibited marginally worse performance compared with controls on the divided attention subtest and significantly worse performance on the selective attention subtest. In the spatial cueing task, they were slower than controls to respond to the presence of the target, particularly when cues were invalid. They were also impaired, relative to controls, on visual search tasks.

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Mizuno K, Watanabe Y. Neurocognitive impairment in childhood chronic fatigue syndrome. Front Physiol. 2013 Apr 19;4:87. PMID: 23626579

Neurocognitive impairment (including reduced attention control in switching and divided-attention tasks) is a feature of childhood chronic fatigue syndrome.

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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. PMID: 23166694

In a cognitive task study, patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive heart rate variability; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge.

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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. PMID: 22440059

This study’s findings suggest that poor effort is unlikely to contribute to cognitive test performance of persons with CFS.

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Constant EL, Adam S, Gillain B, Lambert M, Masquelier E, Seron X. Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls. Clin Neurol Neurosurg. 2011 Jan 19. PMID: 21255911

CFS patients have objective impairments in attention and memory, but with good motivation and without exaggerated suggestibiity.

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Ocon AJ. Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome. Front Physiol. 2013;4:63. PMID: 23576989

The cognitive symptoms of CFS may be due to altered cerebral blood flow activation and regulation that are exacerbated by a stressor, such as orthostasis or a difficult mental task, resulting in the decreased ability to readily process information.

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Kawatani J, Mizuno K, Shiraishi S, Takao M, Joudoi T, Fukuda S, Watanabe Y, Tomoda A. Cognitive dysfunction and mental fatigue in childhood chronic fatigue syndrome – A 6-month follow-up study. Brain Dev. 2011 Apr 27. PMID: 21530119

Higher-order level cognitive dysfunction affects childhood CFS pathogenesis. Alternative attention performance evaluated by the mATMT may be used to monitor improvement in patients with CCFS. Combined treatment with CBT and medication may be effective to improve poor attention characteristics associated with CCFS.

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Kadota Y, Cooper G, Burton AR, Lemon J, Schall U, Lloyd A, Vollmer-Conna U. Autonomic hyper-vigilance in post-infective fatigue syndrome. Biol Psychol. 2010 Sep;85(1):97-103. PMID: 20678991

Post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges.

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Thomas M, Smith A. An investigation into the cognitive deficits associated with chronic fatigue syndrome. Open Neurol J. 2009 Feb 27;3:13-23. PMID: 19452031

CFS patients demonstrate specific cognitive impairments.

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Dickson A, Toft A, O’Carroll RE. Neuropsychological functioning, illness perception, mood and quality of life in chronic fatigue syndrome, autoimmune thyroid disease and healthy participants. Psychol Med. 2009 Sep;39(9):1567-76. PMID: 19144216

The results of this study suggest that the primary cognitive impairment in CFS is attention and that this is not secondary to affective status. The lower treatment control perceptions and greater illness concerns that CFS patients report may be causally related to their affective status.

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Schrijvers D, Van Den Eede F, Maas Y, Cosyns P, Hulstijn W, Sabbe BG. Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study. J Affect Disord. 2009 May;115(1-2):46-53. PMID: 18817977

Patients with CFS or depression demonstrated overall fine motor slowing and similar cognitive impairments.

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Haig-Ferguson A, Tucker P, Eaton N, Hunt L, Crawley E. Memory and attention problems in children with chronic fatigue syndrome or myalgic encephalopathy. Arch Dis Child. 2009 Oct;94(10):757-62. PMID: 19001478

Children with CFS/ME appear to experience problems with attention, which may have adverse implications for verbal memory.

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Majer M, Welberg LA, Capuron L, Miller AH, Pagnoni G, Reeves WC. Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study. Psychosom Med. 2008 Sep;70(7):829-36. PMID: 18606722

CFS patients have alterations in motor speed and working memory independent of comorbid psychiatric disease and medication usage.

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Claypoole KH, Noonan C, Mahurin RK, Goldberg J, Erickson T, Buchwald D. A twin study of cognitive function in chronic fatigue syndrome: the effects of sudden illness onset. Neuropsychology. 2007 Jul;21(4):507-13. PMID: 17605583

In a study of CFS patients and healthy identical twins, patients exhibited decreases in motor functions, speed of information processing, verbal memory, and executive functioning.

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Glass JM. Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions. Curr Rheumatol Rep. 2006 Dec;8(6):425-9. PMID: 17092441

CFS patients often have memory and cognitive complaints. Neuroimaging studies demonstrate cerebral abnormalities and a pattern of increased neural recruitment during cognitive tasks.

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Capuron L, Welberg L, Heim C, Wagner D, Solomon L, Papanicolaou DA, Craddock RC, Miller AH, Reeves WC. Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome. Neuropsychopharmacology. 2006 Aug;31(8):1777-84. PMID: 16395303

This study shows strong concordance between subjective complaints of mental fatigue and objective measurement of cognitive impairment in CFS patients and suggests that mental fatigue is an important component of CFS-related cognitive dysfunction.

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Tanaka M, Sadato N, Okada T, Mizuno K, Sasabe T, Tanabe HC, Saito DN, Onoe H, Kuratsune H, Watanabe Y. Reduced responsiveness is an essential feature of chronic fatigue syndrome: a fMRI study. BMC Neurol. 2006 Feb 22;6:9. PMID: 16504053

CFS may be characterised by attenuation of the responsiveness to stimuli not directly related to the fatigue-inducing task.

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Caseras X, Mataix-Cols D, Giampietro V, Rimes KA, Brammer M, Zelaya F, Chalder T, Godfrey EL. Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task. Psychosom Med. 2006 Nov-Dec;68(6):947-55. PMID: 17079703

Patients with CFS show both quantitative and qualitative differences in activation of the working memory network compared with healthy control subjects.*

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Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Mores J, Natelson BH. Exercise and cognitive performance in chronic fatigue syndrome. Med Sci Sports Exerc. 2005 Sep;37(9):1460-7. PMID: 16177595

CFS patients without comorbid FM exhibit subtle cognitive deficits in terms of speed, consistency, and efficiency that are not improved or exacerbated by light exercise.

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Schillings ML, Kalkman JS, van der Werf SP, van Engelen BG, Bleijenberg G, Zwarts MJ. Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome. Clin Neurophysiol. 2004 Nov;115(11):2518-24. PMID: 15465441

Central activation is diminished in CFS patients. Possible causes include changed perception, impaired concentration, reduced effort and physiologically defined changes, e.g. in the corticospinal excitability or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue.

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Deluca J, Christodoulou C, Diamond BJ, Rosenstein ED, Kramer N, Natelson BH. Working memory deficits in chronic fatigue syndrome: differentiating between speed and accuracy of information processing. J Int Neuropsychol Soc. 2004 Jan;10(1):101-9. PMID: 14751012

Compared to healthy controls (HC) and a group of participants with rheumatoid arthritis (RA), the CFS-noPsych group displayed significantly reduced performance on tests of information processing speed, but not on tests of working memory.

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Davey NJ, Puri BK, Catley M, Main J, Nowicky AV, Zaman R. Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome. Int J Clin Pract. 2003 May;57(4):262-4. PMID: 12800454

This study provides evidence that changing motor deficits in CFS have a neurophysiological basis. The slowness of simple reaction times supports the notion of a deficit in motor preparatory areas of the brain.

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Michiels V, Cluydts R. Neuropsychological functioning in chronic fatigue syndrome: a review. Acta Psychiatr Scand. 2001 Feb;103(2):84-93. PMID: 11167310

The current research shows that slowed processing speed, impaired working memory and poor learning of information are the most prominent features of cognitive dysfunctioning in patients with CFS.

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Friedberg F, Dechene L, McKenzie MJ 2nd, Fontanetta R. Symptom patterns in long-duration chronic fatigue syndrome. J Psychosom Res. 2000 Jan;48(1):59-68. PMID: 10750631

People with long-duration CFS reported a large number of specific cognitive difficulties that were greater in severity than those reported by participants with short-duration CFS. The pattern of comorbid disorders in the CFS groups was consistent with hypersensitivity and viral reactivation hypotheses.

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Michiels V, Cluydts R, Fischler B. Attention and verbal learning in patients with chronic fatigue syndrome. J Int Neuropsychol Soc. 1998 Sep;4(5):456-66. PMID: 9745235

CFS patients were poorer than controls on recall of verbal information.

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Servatius RJ, Tapp WN, Bergen MT, Pollet CA, Drastal SD, Tiersky LA, Desai P, Natelson BH. Impaired associative learning in chronic fatigue syndrome. Neuroreport. 1998 Apr 20;9(6):1153-7. PMID: 9601685

CFS patients displayed impaired acquisition of the eyeblink response using a delayed-type conditioning paradigm. This suggests organic brain dysfunction within a defined neural substrate in CFS patients.

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Michiels V, Cluydts R, Fischler B, Hoffmann G, Le Bon O, De Meirleir K. Cognitive functioning in patients with chronic fatigue syndrome. J Clin Exp Neuropsychol. 1996 Oct;18(5):666-77. PMID: 8941852

The learning rate of verbal and visual material for patients with CFS was slower, and delayed recall of verbal and visual information was impaired, compared to normals. There was a high variability in cognitive impairment within the CFS group. The neuropsychological variables of psychomotor performance and verbal memory were found to discriminate best between patients and controls.

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Marcel B, Komaroff AL, Fagioli LR, Kornish RJ 2nd, Albert MS. Cognitive deficits in patients with chronic fatigue syndrome. Biol Psychiatry. 1996 Sep 15;40(6):535-41. PMID: 8879474

A subset of CFS patients may experience significant impairments in learning and memory.

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Johnson SK, DeLuca J, Diamond BJ, Natelson BH. Selective impairment of auditory processing in chronic fatigue syndrome: a comparison with multiple sclerosis and healthy controls. Percept Mot Skills. 1996 Aug;83(1):51-62. PMID: 8873173

CFS patients are more impaired on auditory than on visual processing tasks.

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Joyce E, Blumenthal S, Wessely S. Memory, attention, and executive function in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1996 May;60(5):495-503. PMID: 8778252

Patients with chronic fatigue syndrome have reduced attentional capacity resulting in impaired performance on effortful tasks requiring planned or self ordered generation of responses from memory.

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Johnson SK, DeLuca J, Fiedler N, Natelson BH. Cognitive functioning of patients with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S84-5. PMID: 8148459

Impaired information processing, rather than primary memory dysfunction, may be at the root of the cognitive problems that afflict so many patients with CFS.

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Sandman CA, Barron JL, Nackoul K, Goldstein J, Fidler F. Memory deficits associated with chronic fatigue immune dysfunction syndrome. Biol Psychiatry. 1993 Apr 15-May 1;33(8-9):618-23. PMID: 8329493

A study of CFS patients revealed significant memory deficits consistent with temporal-limbic dysfunction.

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DeLuca J, Johnson SK, Natelson BH. Information processing efficiency in chronic fatigue syndrome and multiple sclerosis. Arch Neurol. 1993 Mar;50(3):301-4. PMID: 8442710

Subjects with CFS showed significant impairment on a test of complex concentration.

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Scheffers MK, Johnson R Jr, Grafman J, Dale JK, Straus SE. Attention and short-term memory in chronic fatigue syndrome patients: an event-related potential analysis.  Neurology. 1992 Sep;42(9):1667-75. PMID: 1513453

Cognitive impairment in CFS involves response-related processes.

 

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