Category: Cognitive Dysfunction

The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker?

Abstract:

The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale. The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men).

Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p < 0.05). There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men.

Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME.

Source: Murga I, Aranburu L, Gargiulo PA, Gómez-Esteban JC, Lafuente JV. The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker? J Transl Med. 2021 Dec 4;19(1):494. doi: 10.1186/s12967-021-03153-1. PMID: 34863209. https://pubmed.ncbi.nlm.nih.gov/34863209/

Modulatory effects of cognitive exertion on regional functional connectivity of the salience network in women with ME/CFS: A pilot study

Abstract:

Background: A common symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM). Various brain abnormalities have been observed in patients with ME/CFS, especially in insular and limbic areas, but their link with ME/CFS symptoms is still unclear. This pilot study aimed at investigating the association between PEM in ME/CFS and changes in functional connectivity (FC) of two main networks: the salience network (SN) and the default-mode network (DMN).

Methods: A total of 16 women, 6 with and 10 without ME/CFS, underwent clinical and MRI assessment before and after cognitive exertion. Resting-state FC maps of 7 seeds (3 for the SN and 4 for the DMN) and clinical measures of fatigue, pain and cognition were analysed with repeated-measure models. FC-symptom change associations were also investigated.

Results: Exertion induced increases in fatigue and pain in patients with ME/CFS, compared to the control group, while no changes were found in cognitive performance. At baseline, patients showed altered FC between some DMN seeds and frontal areas and stronger FC between all SN seeds and left temporal areas and the medulla. Significantly higher FC increases in patients than in controls were found only between the right insular seed and frontal and subcortical areas; these increases correlated with worsening of symptoms.

Conclusions: Cognitive exertion can induce worsening of ME/CFS-related symptoms. These changes were here associated with strengthening of FC of the right insula with areas involved in reward processing and cognitive control.

Source: Riccardo Manca, Katija Khan, Micaela Mitolo, Matteo DeMarco, Lynsey Grieveson, Rosemary Varley, Iain D. Wilkinson, Annalena Venneri. Journal of the Neurological Sciences Preprint. January 22, 2021. DOI:https://doi.org/10.1016/j.jns.2021.117326 https://www.jns-journal.com/article/S0022-510X(21)00019-8/fulltext#secst0005 

Cognitive Function Declines Following Orthostatic Stress in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Introduction: Orthostatic intolerance (OI) is common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Cognitive dysfunction has been demonstrated during head-up tilt testing (HUT) in those with ME/CFS: worse scores on cognitive tests occur with increasing tilt angles and increasing complexity of the cognitive challenge. The aim of our study was to determine whether cognitive impairment persists after completion of HUT.

Methods and results: Eligible participants were consecutive individuals satisfying criteria for ME/CFS who underwent HUT because of OI. The 2- and 3-back tests were performed before the start of HUT and within 5 min after completion of HUT. We measured the percentage of correct responses and raw reaction times before and after HUT for both the 2- and 3-back tests. We studied 128 ME/CFS patients who underwent HUT and had a complete set of N-back data before and after HUT. Compared to pre-tilt responses, the percentage of correct responses on the 2-back test decreased post-HUT from 77(18) to 62(21) and of the 3-back test from 57(17) to 41(17) (both p < 0.0001). The raw reaction time of the 2-back test increased post-HUT from 783(190) to 941(234) m/s and of the 3-back test from 950(170) to 1102(176) (both p < 0.0001). There was no difference in the N-back test data for subgroups dichotomized based on disease severity, the presence of co-morbid fibromyalgia, or the presence of postural orthostatic tachycardia syndrome.

Conclusion: As measured by the N-back test, working memory remains impaired in adults with ME/CFS following a 30-min head-up tilt test.

Source: van Campen CLMC, Rowe PC, Verheugt FWA, Visser FC. Cognitive Function Declines Following Orthostatic Stress in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Neurosci. 2020;14:688. Published 2020 Jun 26. doi:10.3389/fnins.2020.00688 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332734/ (Full text)

Attentional Processing and Interpretative Bias in Functional Neurological Disorder

Abstract:

Objective: Altered attentional processing (automatically attending to negative or illness-relevant information) and interpretative biases (interpreting ambiguous information as negative or illness-relevant) may be mechanistically involved in functional neurological disorder (FND). Common mechanisms between FND and chronic fatigue syndrome (CFS) have been proposed but not compared experimentally.

Methods: We compared cognitive task performance of FND, CFS and healthy control (HC) groups. Tasks assessed attentional bias towards illness-relevant stimuli (visual probe task), attentional control (attention network task) and somatic interpretations (interpretative bias task), alongside self-reported depression, anxiety, fatigue and general health.

Results: Thirty-seven participants diagnosed with FND, 52 participants diagnosed with CFS and 51 HC participants were included. Whilst participants with CFS showed attentional bias for illness-relevant stimuli relative to HC (t = -3.13 p = 0.002, d = 0.624), individuals with FND did not (t = -1.59, p = 0.118, d = 0.379). Both FND (t = 3.08, p = 0.003, d = 0.759) and CFS (t = 2.74, p = 0.007, d = 0.548) groups displayed worse attentional control than HC. Similarly, FND (t = 3.63, p < 0.001, d = 0.801) and CFS groups (t = 4.58, p < 0.001, d = 0.909) showed more somatic interpretative bias than HC.

Conclusions: Similar attentional control deficits and somatic interpretative bias in individuals with FND and CFS support potential shared mechanisms underlying symptoms. Interpretative bias towards somatic and illness-relevant stimuli in functional disorders may prove a therapeutic target.

Source: Keynejad RC, Fenby E, Pick S, et al. Attentional processing and interpretative bias in functional neurological disorder [published online ahead of print, 2020 Jun 12]. Psychosom Med. 2020;10.1097/PSY.0000000000000821. doi:10.1097/PSY.0000000000000821 https://pubmed.ncbi.nlm.nih.gov/32541544/

Objective Cognitive Performance and Subjective Complaints in Patients With Chronic Q Fever or Q Fever Fatigue Syndrome

Abstract:

Background: Primary aim of this study was to compare cognitive performance of patients with chronic Q fever or Q fever fatigue syndrome (QFS) to matched controls from the general population, while taking performance validity into account. Second, we investigated whether objective cognitive performance was related to subjective cognitive complaints or psychological wellbeing.

Methods: Cognitive functioning was assessed with a neuropsychological test battery measuring the domains of processing speed, episodic memory, working memory and executive functioning. Tests for performance validity and premorbid intelligence were also included. Validated questionnaires were administered to assess self-reported fatigue, depressive symptoms and cognitive complaints.

Results: In total, 30 patients with chronic Q fever, 32 with QFS and 35 controls were included. A high percentage of chronic Q fever patients showed poor performance validity (38%) compared to controls (14%, p = 0.066). After exclusion of participants showing poor performance validity, no significant differences between patients and controls were found in the cognitive domains. QFS patients reported a high level of cognitive complaints compared to controls (41.2 vs 30.4, p = 0.023). Cognitive complaints were not significantly related to cognitive performance in any of the domains for this patient group.

Conclusions: The high level of self-reported cognitive complaints in QFS patients does not indicate cognitive impairment. A large proportion of the chronic Q fever patients showed suboptimal mental effort during neuropsychological assessment. More research into the underlying explanations is needed. Our findings stress the importance of assessing cognitive functioning by neuropsychological examination including performance validity, rather than only measuring subjective cognitive complaints.

Source: Reukers DFM, Aaronson J, van Loenhout JAF, et al. Objective cognitive performance and subjective complaints in patients with chronic Q fever or Q fever fatigue syndrome. BMC Infect Dis. 2020;20(1):397. Published 2020 Jun 5. doi:10.1186/s12879-020-05118-z https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275429/ (Full text)

 

The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients

[Editor’s Note: The dropout rate for this study was 50%. After false discovery rate (FDR) correction, none the results achieved statistical significance.]

Abstract:

BACKGROUND: Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined.

METHODS: Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times) and Choice Reaction Time (CRT) measurements, a Visual Attention Test (VAT) and a Delayed Matching to Sample (DMS) assessment.

RESULTS: Statistically significant improvement was noted in the third attempt to SRT in reaction time for correct answers, p = 0.045, r = 0.24. Moreover, significant improvement was noted in VAT reaction time, number of correct answers and errors committed, p = 0.02, omega = 0.03, p = 0.007, r = 0.34 and p = 0.004, r = 0.35, respectively. Non-significant changes were noted in other cognitive tests.

CONCLUSIONS: A substantial number of participants were unwilling or unable to complete the exercise programme. ME/CFS patients able to complete the SEP showed improved visual attention both in terms of reaction time and correctness of responses and processing speed of simple visual stimuli.

Source: Zalewski P1, Kujawski S1, Tudorowska M2, Morten K3, Tafil-Klawe M4, Klawe JJ1, Strong J3, Estévez-López F5, Murovska M6, Newton JL7, The European Network On Me/Cfs Euromene. The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients. Brain Sci. 2019 Dec 19;10(1). pii: E4. doi: 10.3390/brainsci10010004. https://www.mdpi.com/2076-3425/10/1/4 (Full study)

Neuropsychological dysfunction in chronic fatigue syndrome and the relation between objective and subjective findings

Abstract:

OBJECTIVE: This study aimed to explore the relationship between self-reported cognitive difficulties, objective neuropsychological test performances, and subjective health complaints in chronic fatigue syndrome (CFS) and to examine the degree of impaired cognitive functions.

METHOD: A total of 236 consecutively recruited outpatients, 18-62 years of age, completed the tests. Self-administered questionnaires were used for assessing fatigue, pain, depression, anxiety and subjective cognitive complaints (Everyday Memory Questionnaire [EMQ]). Also, neuropsychological tests, that is, Stroop I-IV, California Verbal Learning Test-Second Edition (CVLT-II) learning and delay, Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) Letter Number (L-N) Sequencing, and the Paced Auditory Serial Addition Task were performed to examine whether these objective measures correlated with subjective complaints and were compared with normative data.

RESULTS: There was a trend of association (p < .05) between the unadjusted EMQ with Stroop IV (inhibition and shifting attention), the CVLT-II learning and delay (verbal learning and memory), and the WAIS-III L-N Sequencing (working memory), but none were statistically significant at the .001 level. The EMQ was positively associated with fatigue, pain, and depression (p < .001). The PASAT (working memory) was negatively associated with pain (p < .001). Between 21% and 38% of the patients performed below the 1.5-SD cutoff for clinically significant impairment on the Stroop tests.

CONCLUSION: The self-reported cognitive performance was not strongly associated with the objective cognitive performances on any domains in patients with CFS. Patients with higher fatigue, pain, and depression levels reported greater subjective cognitive difficulties, as well as higher pain related to lower objective working memory function. The CFS patients had problems mainly in the domains of psychomotor speed and attention measured by the objective neuropsychological tests. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

TRIAL REGISTRATION: ClinicalTrials.gov NCT00920777.

Source: Rasouli O, Gotaas ME, Stensdotter AK, Skovlund E, Landrø NI, Dåstøl P, Fors EA. Neuropsychological dysfunction in chronic fatigue syndrome and the relation between objective and subjective findings. Neuropsychology. 2019 Jun 6. doi: 10.1037/neu0000550. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31169386

Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome

Abstract:

Emerging evidence suggests that central nervous system dysfunction may underlie the core symptoms of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in adults, such as cognitive disturbance, fatigue and post-exertional malaise. Research into brain dysfunction in the pediatric CFS/ME context, however, is severely lacking. It is unclear whether the adolescent CFS/ME brain functions differently compared with healthy peers, particularly in situations where significant mental effort is required. This study used resting-state functional MRI in a novel repeated-measures design to evaluate intrinsic connectivity, cognitive function, and subjective fatigue, before and after a period of cognitive exertion in 48 adolescents (25 CFS/ME, 23 healthy controls).

Results revealed little evidence for a differential effect of cognitive exertion in CFS/ME compared with controls. Both groups demonstrated a similar rate of reduced intrinsic functional connectivity within the default mode network (DMN), reduced sustained attentional performance, slower processing speed, and increased subjective fatigue as a result of cognitive exertion.

However, CFS/ME adolescents consistently displayed higher subjective fatigue, and controls outperformed the CFS/ME group overall on cognitive measures of processing speed, sustained attention and new learning. No brain-behavior relationships were observed between DMN connectivity, cognitive function, and fatigue over time.

These findings suggest that effortful cognitive tasks may elicit similar levels of energy expenditure across all individuals in the form of reduced brain functioning and associated fatigue. However, CFS/ME may confer a lower starting threshold from which to access energy reserves and cognitive resources when cognitive effort is required.

Source: Josev EK, Malpas CB, Seal ML, Scheinberg A6, Lubitz L, Rowe K, Knight SJ. Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome. Brain Imaging Behav. 2019 May 17. doi: 10.1007/s11682-019-00119-2. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31102168

Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction

Abstract:

OBJECTIVES: To explore cognitive performance in chronic fatigue syndrome (CFS) examining two cohorts. To establish findings associated with CFS and those related to co-morbid depression or autonomic dysfunction.

METHODS: Identification and recruitment of participants was identical in both phases, all CFS patients fulfilled Fukuda criteria. In Phase 1 (n = 48) we explored cognitive function in a heterogeneous cohort of CFS patients, investigating links with depressive symptoms (HADS). In phase 2 (n = 51 CFS & n = 20 controls) participants with co-morbid major depression were excluded (SCID). Furthermore, we investigated relationships between cognitive performance and heart rate variability (HRV).

RESULTS: Cognitive performance in unselected CFS patients is in average range on most measures. However, 0-23% of the CFS sample fell below the 5th percentile. Negative correlations occurred between depressive symptoms (HAD-S) with Digit-Symbol-Coding (r = -.507, p = .006) and TMT-A (r = -.382, p = .049). In CFS without depression, impairments of cognitive performance remained with significant differences in indices of psychomotor speed (TMT-A: p = 0.027; digit-symbol substitution: p = 0.004; digit-symbol copy: p = 0.007; scanning: p = .034) Stroop test suggested differences due to processing speed rather than inhibition. Both cohorts confirmed relationships between cognitive performance and HRV (digit-symbol copy (r = .330, p = .018), digit-symbol substitution (r = .313, p = .025), colour-naming trials Stroop task (r = .279, p = .050).

CONCLUSION: Cognitive difficulties in CFS may not be as broad as suggested and may be restricted to slowing in basic processing speed. While depressive symptoms can be associated with impairments, co-morbidity with major depression is not itself responsible for reductions in cognitive performance. Impaired autonomic control of heart-rate associates with reductions in basic processing speed.

Source: Robinson LJ, Gallagher P, Watson S, Pearce R, Finkelmeyer A, Maclachlan L, Newton JL. Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction. PLoS One. 2019 Feb 5;14(2):e0210394. doi: 10.1371/journal.pone.0210394. eCollection 2019. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210394 (Full article)

Feedback on underperformance in patients with Chronic Fatigue Syndrome: The impact on subsequent neuropsychological test performance

Abstract:

Performance Validity Tests (PVTs) are used to measure the credibility of neuropsychological test results. Until now, however, a minimal amount is known about the effects of feedback upon noncredible results (i.e., underperformance) on subsequent neuropsychological test performance.

The purpose of this study was to investigate the effects of feedback on underperformance in Chronic Fatigue Syndrome (CFS) patients. A subset of these patients received feedback on Amsterdam Short-Term Memory (ASTM) failure (i.e., feedback [FB] group). After matching, the final sample consisted of two comparable groups (i.e., FB and No FB; both n = 33). At baseline and follow-up assessment, the patients completed the ASTM and two measurements of information processing speed (Complex Reaction Time [CRT] and Symbol Digit Test [SDT]).

Results indicated that the patients in the FB group improved significantly on the CRT, compared to the No FB group. Although not significant, a comparable trend-like effect was observed for the SDT. Independent of the feedback intervention there was a substantial improvement on ASTM performance at re-administration. A limited feedback intervention upon underperformance in CFS patients may result in improvement on information processing speed performance. This implies that such an intervention might be clinically relevant, since it maximizes the potential of examining the patients’ actual level of cognitive abilities.

Source: Roor JJ, Knoop H, Dandachi-FitzGerald B, Peters MJV, Bleijenberg G, Ponds RWHM. Feedback on underperformance in patients with Chronic Fatigue Syndrome: The impact on subsequent neuropsychological test performance. Appl Neuropsychol Adult. 2018 Oct 31:1-9. doi: 10.1080/23279095.2018.1519509. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30380922