Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter

Abstract:

BACKGROUND: In addition to the frequently reported pain complaints, performance-based cognitive capabilities in patients with chronic fatigue syndrome (CFS) with and without comorbid fibromyalgia (FM) are significantly worse than those of healthy controls. In various chronic pain populations, cognitive impairments are known to be related to pain severity. However, to the best of our knowledge, the association between cognitive performance and experimental pain measurements has never been examined in CFS patients.

OBJECTIVES: This study aimed to examine the association between cognitive performance and self-reported as well as experimental pain measurements in CFS patients with and without FM.

STUDY DESIGN: Observational study.

SETTING: The present study took place at the Vrije Universiteit Brussel and the University of Antwerp.

METHODS: Forty-eight (18 CFS-only and 30 CFS+FM) patients and 30 healthy controls were studied. Participants first completed 3 performance-based cognitive tests designed to assess selective and sustained attention, cognitive inhibition, and working memory capacity. Seven days later, experimental pain measurements (pressure pain thresholds [PPT], temporal summation [TS], and conditioned pain modulation [CPM]) took place and participants were asked to fill out 3 questionnaires to assess self-reported pain, fatigue, and depressive symptoms.

RESULTS: In the CFS+FM group, the capacity of pain inhibition was significantly associated with cognitive inhibition. Self-reported pain was significantly associated with simple reaction time in CFS-only patients. The CFS+FM but not the CFS-only group showed a significantly lower PPT and enhanced TS compared with controls.

LIMITATIONS: The cross-sectional nature of this study does not allow for inferences of causation.

CONCLUSIONS: The results underline disease heterogeneity in CFS by indicating that a measure of endogenous pain inhibition might be a significant predictor of cognitive functioning in CFS patients with FM, while self-reported pain appears more appropriate to predict cognitive functioning in CFS patients without FM.

 

Source: Ickmans K, Meeus M, De Kooning M, Lambrecht L, Pattyn N, Nijs J. Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter. Pain Physician. 2015 Sep-Oct;18(5):E841-52. http://www.painphysicianjournal.com/current/pdf?article=MjQxOA%3D%3D&journal=91 (Full article as PDF file)

 

The impact of chronic fatigue syndrome on cognitive functioning in adolescents

Abstract:

Chronic fatigue syndrome (CFS) is characterized by persistent fatigue and severe disability. Most adolescent patients report attention and concentration problems, with subsequent poor performance at school. This study investigated the impact of CFS on intellectual capacity by (1) assessing discrepancies between current intelligence quotient (IQ) and school level and (2) exploring differences in current IQ and pre-CFS school performance, compared with healthy individuals. Current data was cross-sectionally gathered and compared with retrospective pre-CFS school performance data. Fifty-nine CFS adolescents and 40 controls were evaluated on performance on age-appropriate intelligence tests and school level. 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. Healthy controls did not show any discrepancies.

CONCLUSION: According to their pre-CFS intelligence assessments, CFS patients started with appropriate secondary school levels at the age of 12. Our data suggest that CFS may be accompanied by a decline in general cognitive functioning. Given the critical age for intellectual development, we recommend a timely diagnosis followed by appropriate treatment of CFS in adolescents.

WHAT IS KNOWN: Adolescent chronic fatigue syndrome (CFS) is a debilitating condition with major impact on social and intellectual development. Most patients report concentration problems, with subsequent poor performance at school. Little is known about the influence of CFS on intellectual performances.

WHAT IS NEW: IQ scores of CFS adolescents are lower than the IQ scores of healthy peers with an equivalent school level. There is a decrease in intelligence performance across time when current IQ scores are compared with pre-CFS cognitive achievement. Healthy controls do not show any discrepancies between their current IQ, school level and previous cognitive functioning. This suggest that adolescent CFS may be accompanied by a decline in general cognitive functioning.

 

Source: 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. doi: 10.1007/s00431-015-2626-1. Epub 2015 Sep 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724362/ (Full article)

 

Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study

Abstract:

OBJECTIVE: Patients with myalgic encephalomyelitis/chronic fatigue syndrome experience cognitive difficulties. The aim of this study was to evaluate the effect of computerized training on working memory in this syndrome.

DESIGN: Non-randomized (quasi-experimental) study with no-treatment control group and non-equivalent dependent variable design in a myalgic encephalomyelitis/chronic fatigue syndrome-cohort.

SUBJECTS: Patients with myalgic encephalomyelitis/chronic fatigue syndrome who participated in a 6-month outpatient rehabilitation programme were included in the study. Eleven patients who showed signs of working memory deficit were recruited for additional memory training and 12 patients with no working memory deficit served as controls.

METHODS: Cognitive training with computerized working memory tasks of increasing difficulty was performed 30-45 min/day, 5 days/week over a 5-week period. Short-term and working memory tests (Digit Span – forward, backward, total) were used as primary outcome measures. Nine of the 11 patients were able to complete the training.

RESULTS: Cognitive training increased working memory (p = 0.003) and general attention (p = 0.004) to the mean level. Short-term memory was also improved, but the difference was not statistically significant (p = 0.052) vs prior training. The control group did not show any significant improvement in primary outcome measures.

CONCLUSION: Cognitive training may be a new treatment for patients with myalgic encephalomyelitis/chronic fatigue syndrome.

 

Source: Maroti D, Westerberg AF, Saury JM, Bileviciute-Ljungar I. Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study. J Rehabil Med. 2015 Aug 18;47(7):665-8. doi: 10.2340/16501977-1976. https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-1976 (Full article)

 

The association between daytime napping and cognitive functioning in chronic fatigue syndrome

Abstract:

OBJECTIVES: The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length) and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience.

METHODS: 118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire), and mood (Hospital Anxiety and Depression Scale).

RESULTS: Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p <.001). Being male, higher depression and more afternoon naps predicted 25.6% of the variance in objective cognitive dysfunction (p <.001). Higher anxiety and depression and morning napping predicted 32.2% of the variance in subjective cognitive dysfunction (p <.001). When patients were classified into groups of mild and moderate sleepiness, those with longer daytime naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group.

CONCLUSIONS: Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management strategies.

 

Source: 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 Jan 9;10(1):e0117136. doi: 10.1371/journal.pone.0117136. ECollection 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289075/ (Full article)

 

Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study

Abstract:

This study examines neuropsychological impairments associated with chronic fatigue syndrome (CFS) and explores their association with related clinical factors.

Sixty-eight women with CFS were assessed with a neuropsychological battery. Raw scores were adjusted for age and gender and were converted to T scores according to normative data extracted from a local sample of 250 healthy subjects. Neuropsychological dysfunction was calculated using summary impairment indexes (proportion of test scores outside normal limits-T score <40-for each cognitive domain). Finally, a linear regression was calculated to identify predictors of cognitive deficit, including intrinsic factors of the disease (level of fatigue and length of illness) and extrinsic factors (emotional factors, age, and education).

Approximately 50% of scores showed impairment in attention and motor functioning, and nearly 40% showed impairment in speed information processing and executive functioning. Fatigue predicted attention and executive functioning impairment, and emotional factors predicted verbal memory dysfunction.

According to our findings, cognitive dysfunction in CFS could be explained by pathophysiological processes of the disease. One implication of this would be the need to identify homogeneous subgroups of patients with CFS by taking into account common factors, which, in turn, would help to identify more specific cognitive profiles, which could then serve to implement appropriate therapeutic measures accordingly.

 

Source: 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. Appl Neuropsychol Adult. 2014;21(2):120-7. doi: 10.1080/09084282.2013.771264. Epub 2013 Aug 13. https://www.ncbi.nlm.nih.gov/pubmed/24826505

 

Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by persistent emotional, mental, and physical fatigue accompanied by a range of neurological, autonomic, neuroendocrine, immune, and sleep problems. Research has shown that psychosocial factors such as anxiety and depression as well as the symptoms of the illness, have a significant impact on the quality of life of people with ME/CFS. In addition, individuals may suffer from deficits in memory and concentration. This study set out to explore the relationships between variables which have been found to contribute to cognitive performance, as measured by prospective and retrospective memory, and cognitive failures.

METHODS: Eighty-seven people with ME/CFS answered questionnaires measuring fatigue, depression, anxiety, social support, and general self-efficacy. These were used in a correlational design (multiple regression) to predict cognitive function (self-ratings on prospective and retrospective memory), and cognitive failures.

RESULTS: Our study found that fatigue, depression, and general self-efficacy were directly associated with cognitive failures and retrospective (but not prospective) memory.

CONCLUSION: Although it was not possible in this study to determine the cause of the deficits, the literature in this area leads us to suggest that although the pathophysiological mechanisms of ME/CFS are unclear, abnormalities in the immune system, including proinflammatory cytokines, can lead to significant impairments in cognition. We suggest that fatigue and depression may be a result of the neurobiological effects of ME/CFS and in addition, that the neurobiological effects of the illness may give rise to both fatigue and cognitive deficits independently.

 

Source: 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 Feb 25;7:67-76. doi: 10.2147/PRBM.S50645. ECollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940708/ (Full article)

 

Rebuttal to Ickmans et al. association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome

Dear Editor:

In a study recently published in Journal of Rehabilitation Research and Development, Ickmans et al. [1] found a substantially deteriorated physical exercise capacity in myalgic encephalopathy/chronic fatigue syndrome (ME/CFS), as established by a cardiopulmonary exercise test (peak oxygen uptake [VO2max]: 19.1 ± 4.6 mL/min/kg, peak heart rate: 145.1 ± 22.4 beats per minute [bpm], peak workload: 114.2 ± 31.3 W, compared with 27.2 ± 5.6 mL/min/ kg, 170.0 ± 36.2 bpm, and 114.2 ± 31.3 W, respectively, in sedentary controls). Ickmans et al. Also observed various cognitive deficits in ME/CFS, e.g., prolonged choice and simple reaction times in various Stroop subtests and the psychomotor vigilance task test (PVT), more errors of omission in the PVT, and worse letter recall scores on the operation span task test, indicative for working memory impairment and reduced psychomotor speed.

You can read the rest of this letter here:  http://www.rehab.research.va.gov/jour/2013/509/pdf/pagevii.pdf 

Comment onAssociation between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome. [J Rehabil Res Dev. 2013]

 

Source: Twisk F. Rebuttal to Ickmans et al. association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome. J Rehabil Res Dev. 2013;50(9):vii-viii. http://www.rehab.research.va.gov/jour/2013/509/pdf/pagevii.pdf (Full article)

 

Cognitive functioning in people with chronic fatigue syndrome: a comparison between subjective and objective measures

Abstract:

OBJECTIVE: The purpose of this study was to examine the relationship between subjective and objective assessments of memory and attention in people with chronic fatigue syndrome (CFS), using tests that have previously detected deficits in CFS samples and measures of potential confounds.

METHOD: Fifty people with CFS and 50 healthy controls were compared on subjective (memory and attention symptom severity, Cognitive Failures Questionnaire, Everyday Attention Questionnaires) and objective (California Verbal Learning Test, Rey-Osterreith Complex Figure Test, Paced Auditory Serial Addition Test, Stroop task) measures of memory and attention. Fatigue, sleep, depression, and anxiety were also assessed.

RESULTS: The CFS group reported experiencing more cognitive problems than the controls, but the two groups did not differ on the cognitive tests. Scores on the subjective and objective measures were not correlated in either group. Depression was positively correlated with increased severity of cognitive problems in both the CFS and control groups.

CONCLUSIONS: There is little evidence for a relationship between subjective and objective measures of cognitive functioning for both people with CFS and healthy controls, which suggests that they may be capturing different constructs. Problems with memory and attention in everyday life are a significant part of CFS. Depression appears to be related to subjective problems but does not fully explain them.

 

Source: Cockshell SJ, Mathias JL. Cognitive functioning in people with chronic fatigue syndrome: a comparison between subjective and objective measures. Neuropsychology. 2014 May;28(3):394-405. doi: 10.1037/neu0000025. Epub 2013 Dec 23. https://www.ncbi.nlm.nih.gov/pubmed/24364389

 

Can recovery of peripheral muscle function predict cognitive task performance in chronic fatigue syndrome with and without fibromyalgia?

Abstract:

BACKGROUND: Both good physical and cognitive functioning have a positive influence on the execution of activities of daily living. Patients with chronic fatigue syndrome (CFS) as well as patients with fibromyalgia have marked cognitive deficits. Furthermore, a good physical and functional health status may have a positive impact on a variety of cognitive skills-a link that has been observed in young and old individuals who are healthy, although evidence is limited in patients with CFS.

OBJECTIVE: The purpose of this study was to examine whether recovery of upper limb muscle function could be a significant predictor of cognitive performance in patients with CFS and in patients with CFS and comorbid fibromyalgia. Furthermore, this study determined whether cognitive performance is different between these patient groups.

DESIGN: A case-control design was used.

METHODS: Seventy-eight participants were included in the study: 18 patients with CFS only (CFS group), 30 patients with CFS and comorbid fibromyalgia (CFS+FM group), and 30 individuals who were healthy and inactive (control group) were studied. Participants first completed 3 performance-based cognitive tests designed to assess selective and sustained attention, cognitive inhibition, and working memory capacity. Seven days later, they performed a fatiguing upper limb exercise test, with subsequent recovery measures.

RESULTS: Recovery of upper limb muscle function was found to be a significant predictor of cognitive performance in patients with CFS. Participants in the CFS+FM group but not those in the CFS group showed significantly decreased cognitive performance compared with the control group.

LIMITATIONS: The cross-sectional nature of this study does not allow for inferences of causation.

CONCLUSIONS: The results suggest that better physical health status could predict better mental health in patients with CFS. Furthermore, they underline disease heterogeneity, suggesting that reducing this factor in future research is important to better understand and uncover mechanisms regarding the nature of diverse impairments in these patients.

 

Source: 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 Apr;94(4):511-22. doi: 10.2522/ptj.20130367. Epub 2013 Dec 20. https://www.ncbi.nlm.nih.gov/pubmed/24363336

 

Association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome.

Abstract:

Limited scientific evidence suggests that physical activity is directly related to cognitive performance in patients with chronic fatigue syndrome (CFS). To date, no other study has examined the direct relationship between cognitive performance and physical fitness in these patients.

This study examined whether cognitive performance and physical fitness are associated in female patients with CFS and investigated the association between cognitive performance and physical activity level (PAL) in the same study sample. We hypothesized that patients who performed better on cognitive tasks would show increased PALs and better performance on physical tests.

The study included 31 women with CFS and 13 healthy inactive women. Participants first completed three cognitive tests. Afterward, they undertook a test to determine their maximal handgrip strength, performed a bicycle ergometer test, and were provided with an activity monitor.

In patients with CFS, lower peak oxygen uptake and peak heart rate were associated with slower psychomotor speed (p < 0.05). Maximal handgrip strength was correlated with working memory performance (p < 0.05). Both choice and simple reaction time were lower in patients with CFS relative to healthy controls (p < 0.05 and p < 0.001, respectively). In conclusion, physical fitness, but not PAL, is associated with cognitive performance in female patients with CFS.

Comment in

 

Source: Ickmans K, Clarys P, Nijs J, Meeus M, Aerenhouts D, Zinzen E, Aelbrecht S, Meersdom G, Lambrecht L, Pattyn N. 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. http://www.rehab.research.va.gov/jour/2013/506/page795.html (Full article)