Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by heterogeneous symptoms, which lack specific biomarkers for its diagnosis. This study aimed to investigate plasma neurofilament light chain (NfL) levels as a potential biomarker for ME/CFS and explore associations with cognitive, autonomic, and neuropathic symptoms.

Here, 67 ME/CFS patients and 43 healthy controls (HCs) underwent comprehensive assessments, including neuropsychological evaluation, autonomic nervous system (ANS) testing, and plasma NfL level analysis. ME/CFS patients exhibited significantly higher plasma NfL levels compared to HC (F = 4.30, p < 0.05). Correlations were observed between NfL levels and cognitive impairment, particularly in visuospatial perception (r = -0.42; p ≤ 0.001), verbal memory (r = -0.35, p ≤ 0.005), and visual memory (r = -0.26; p < 0.05) in ME/CFS. Additionally, higher NfL levels were associated with worsened autonomic dysfunction in these patients, specifically in parasympathetic function (F = 9.48, p ≤ 0.003).

In ME/CFS patients, NfL levels explained up to 17.2% of the results in cognitive tests. Unlike ME/CFS, in HC, NfL levels did not predict cognitive performance. Elevated plasma NfL levels in ME/CFS patients reflect neuroaxonal damage, contributing to cognitive dysfunction and autonomic impairment.

These findings support the potential role of NfL as a biomarker for neurological dysfunction in ME/CFS. Further research is warranted to elucidate underlying mechanisms and clinical implications.

Source: Azcue N, Tijero-Merino B, Acera M, Pérez-Garay R, Fernández-Valle T, Ayo-Mentxakatorre N, Ruiz-López M, Lafuente JV, Gómez Esteban JC, Del Pino R. Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Biomedicines. 2024 Jul 11;12(7):1539. doi: 10.3390/biomedicines12071539. PMID: 39062112; PMCID: PMC11274366. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11274366/ (Full text)

Patients with Fibromyalgia Scored Worse in Memory, Attention, Cognitive Function

Press release:

A cross-sectional study demonstrated significant impairments in attention, memory, and higher cognitive functions among a cohort of patients with fibromyalgia and rheumatoid arthritis (RA), according to a study published in Psychology Research and Behavior Management.1

Investigators believe deficits in the fibromyalgia cohort could be explained by secondary symptoms coupled with more severe pain. A cognitive screening could help curate personalized treatment plans to improve the quality of life among patients with RA and fibromyalgia.

“Research directly comparing cognitive performance between patients with fibromyalgia and RA is still scarce. Some studies suggested deficits of similar magnitude in both patient groups,” wrote a group of investigators led by Carmen María Galvez Sánchez, PhD, associated with the Department of Personality, Evaluation and Psychological Treatment at the University of Murcia, Spain. “In response to this exigency, there is a requisite for the evaluation of cognitive impairments in individuals with chronic pain, aiming to formulate and implement interventions rooted in neuropsychological training. This approach is intended to ameliorate cognitive performance and mitigate its consequential impact on health-related quality of life.”

In certain patients with fibromyalgia, cognitive impairment was linked to clinical pain severity, depression, fatigue, insomnia, and anxiety. Similarly, these were also reported in patients with RA, although pain and emotional symptoms within the fibromyalgia cohort.2 Symptoms of fibromyalgia and RA often include depression, fatigue, insomnia, and cognitive issues.

Investigators analyzed the performance in cognitive domains between patients with RA and fibromyalgia using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Questionnaire scores were combined to determine the symptom severity factor, which was used as a control variable within the group comparisons.

A total of 64 patients with fibromyalgia, 34 patients with RA, and 32 healthy controls were included in the study. All patients were female.

Without controlling for the severity of symptoms, patients with either fibromyalgia or RA performed worse when compared with controls in terms of cognitive domains including verbal memory, visual memory, and strategic planning.

Additionally, over deficits were observed in the fibromyalgia cohort compared with RA. Patients with fibromyalgia reported more severe symptoms, such as pain intensity, total pain, anxiety, depression, insomnia, and fatigue, compared with patients with RA. After controlling for symptom severity a significant proportion of cognitive test, a large proportion of cognitive test parameters were not different between rheumatologic cohorts.

Limitations included the lack of information regarding the influence of psychotropic and pain medication on cognitive performance among rheumatic patients. Although the limitation could have been determined using subgroup analysis, the current sample size was too small to form these subgroups.

Further, no data on treatment and disease activity were collected in the RA subgroup and the analysis of the effects of clinical symptoms on cognitive performance was limited. Additionally, not all psychological factors that may impact cognition were assessed in the analysis. The generalizability of findings may be hindered as only women were included in the analysis and the recruitment of subjects was not randomly performed. Lastly, the RA and fibromyalgia diagnoses were performed by different rheumatologists, which may have introduced selection bias.

“Based on the present results, it is recommended that screening for cognitive deficits be part of routine diagnostics for fibromyalgia and RA, which may help to guide the design of personalized interventions to optimize cognitive performance of patients with fibromyalgia and RA,” investigators concluded.

Source: Lana Pine. HCP Live.

Characterization of neurocognitive deficits in patients with post-COVID-19 syndrome: persistence, patients’ complaints, and clinical predictors.

Abstract:

Introduction: Cognitive symptoms persisting beyond 3 months following COVID-19 present a considerable disease burden. We aimed to establish a domain-specific cognitive profile of post-COVID-19 syndrome (PCS). We examined the deficits’ persistence, relationships with subjective cognitive complaints, and clinical variables, to identify the most relevant cognitive deficits and their predictors.

Methods: This cross-sectional study examined cognitive performance and patient-reported and clinical predictors of cognitive deficits in PCS patients (n = 282) and socio-demographically comparable healthy controls (n = 52).

Results: On the Oxford Cognitive Screen-Plus, the patient group scored significantly lower in delayed verbal memory, attention, and executive functioning than the healthy group. In each affected domain, 10 to 20% of patients performed more than 1.5 SD below the control mean. Delayed memory was particularly affected, with a small effect of hospitalization and age. Attention scores were predicted by hospitalization and fatigue.

Discussion: Thus, PCS is associated with long-term cognitive dysfunction, particularly in delayed memory, attention, and executive functioning. Memory deficits seem to be of particular relevance to patients’ experience of subjective impairment. Hospitalization, fatigue, and age seem to predict cognitive deficits, while time since infection, depression, and pre-existing conditions do not.

Source: Kozik V, Reuken P, Utech I, Gramlich J, Stallmach Z, Demeyere N, Rakers F, Schwab M, Stallmach A, Finke K. Characterization of neurocognitive deficits in patients with post-COVID-19 syndrome: persistence, patients’ complaints, and clinical predictors. Front Psychol. 2023 Oct 17;14:1233144. doi: 10.3389/fpsyg.2023.1233144. PMID: 37915528; PMCID: PMC10616256. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616256/ (Full text)

Cognitive-linguistic difficulties in adults with Long COVID: A follow-up study

Abstract:

As the emergency phase of the COVID-19 pandemic subsides, the long-term health problems caused by SARS-CoV-2 infection are becoming increasingly clear. So-called Long COVID, or post COVID-19 condition, is a debilitating illness that impacts functioning for months and even years after infection. Alongside physical symptoms, Long COVID has a particularly insidious effect on cognition and language. While many studies have documented non-linguistic cognitive impairments in people with Long COVID, what has not been documented to any significant extent is the presence and duration of language difficulties in Long COVID. This study addresses this lack of research by examining the cognitive-linguistic skills of 41 adults with Long COVID.

These adults were assessed at two time points using a test protocol of 12 language tasks. This paper describes the findings of the 6-month follow-up study. Results indicate that difficulties in immediate and delayed verbal recall persist long after the onset of COVID symptoms, even as improvements occur in verbal fluency and the informativeness of spoken discourse.

It is argued that these difficulties are a significant contributing factor in a lack of work return in these adults. Implications of these findings for the provision of speech-language pathology services to these adults and occupational health policies relating to Long COVID are discussed.

Source: Louise Cummings. Cognitive-linguistic difficulties in adults with Long COVID: A follow-up study. Language and Health. Available online 2 October 2023. https://www.sciencedirect.com/science/article/pii/S2949903823000325 (Full text)

Memory and attention problems in children with chronic fatigue syndrome or myalgic encephalopathy

Abstract:

OBJECTIVE: To understand more about the problems children with chronic fatigue syndrome (CFS) or myalgic encephalopathy (ME) experience with memory and attention, and to test the feasibility of quantitative measurement of both memory and attention.

DESIGN: Four-item semistructured questionnaire and neuropsychological test battery with 10 psychometric subtests.

SETTING: Family home of the child taking part.

PATIENTS: 20 children with a diagnosis of CFS/ME experiencing memory and/or concentration problems were recruited between April and October 2007 from a regional CFS/ME clinical service (female 13; average age 13.5 years; range 8-16).

METHODS: Each child, parent and teacher was asked to describe the child’s memory and attention problems. Responses were subject to thematic analysis by two independent researchers. In addition, each child completed a battery of 10 tests to measure: processing speed; attention; immediate and delayed memory; working memory; executive function. Raw scores were converted into age-scaled scores and the children’s psychometric scores on the 10 tests taken were compared with normative data using t tests.

RESULTS: Children with CFS/ME, their parents and teachers described problems with focussed attention, sustained attention, recall and stress. Scores for sustained attention (mean 8.1, 95% CI 6.3 to 9.9), switching attention (7.5, 5.5 to 9.4), divided attention (6.9, 5.5 to 8.2), auditory learning (8.2, 6.8 to 9.6) and immediate recall (8.7, 7.3 to 10.0) appeared lower than the normative mean of 10.

CONCLUSIONS: Children with CFS/ME appear to experience problems with attention, which may have adverse implications for verbal memory. These cognitive problems may explain some of the educational difficulties associated with CFS.

 

Source: 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. doi: 10.1136/adc.2008.143032. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19001478

 

Cognitive functioning in patients with chronic fatigue syndrome

Abstract:

A comprehensive battery of neuropsychological tests was administered to 35 outpatients suffering from Chronic Fatigue Syndrome (CFS). They were compared to 33 normal controls matched for age, gender, intelligence, and education.

The patients displayed psychomotor slowing and impaired attention. The learning rate of verbal and visual material for patients with CFS was slower, and delayed recall of verbal and visual information was impaired. Because there was a high variability in cognitive impairment within the CFS group, it would be inappropriate to generalize results to the entire CFS population. Two neuropsychological variables indicating aspects of psychomotor performance and verbal memory were found to discriminate best between patients and controls.

 

Source: 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. http://www.ncbi.nlm.nih.gov/pubmed/8941852

 

Neuropsychological and psychiatric abnormalities in myalgic encephalomyelitis: a preliminary report

Abstract:

Ten patients attending one general medical hospital clinic who fulfilled operational criteria for the diagnosis of myalgic encephalomyelitis (ME) and with a history longer than three months, underwent a series of standardized neuropsychological and psychiatric tests. Nine were able to complete the tests and were individually matched with a normal control group for age, sex, educational background and premorbid intelligence. The ME subjects showed inferior performance to the controls on two tests of verbal memory. Their personality scores displayed less extraversion and less psychoticism. This is the first report of objective neuropsychological abnormalities in patients with ME, suggesting a discrete deterioration of short-term memory. The findings may also suggest a concurrent psychiatric component of the condition, but the direction of causality remains to be clarified.

 

Source: Riccio M, Thompson C, Wilson B, Morgan DJ, Lant AF. Neuropsychological and psychiatric abnormalities in myalgic encephalomyelitis: a preliminary report. Br J Clin Psychol. 1992 Feb;31 ( Pt 1):111-20. http://www.ncbi.nlm.nih.gov/pubmed/1559114