Tag: working memory

A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation

Abstract:

Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological disorder characterized by post-exertional malaise. Despite its clinical relevance, the disease mechanisms of ME/CFS are not fully understood. The previous studies targeting brain function or metabolites have been inconclusive in understanding ME/CFS complexity. We combined single-voxel magnetic resonance spectroscopy (SV-MRS) and functional magnetic resonance imaging (fMRI). Our objectives were to examine the feasibility of the multimodal MRI protocol, identify possible differences between ME/CFS and healthy controls (HCs), and relate MRI findings with clinical symptoms.

Methods: We enrolled 18 female ME/CFS participants (mean age: 39.7 ± 12.0 years) and five HCs (mean age: 45.6 ± 14.5 years). SV-MRS spectra were acquired from three voxels of interest: the anterior cingulate gyrus (ACC), brainstem (BS), and left dorsolateral prefrontal cortex (L-DLPFC). Whole-brain fMRI used n-back task testing working memory and executive function. The feasibility was assessed as protocol completion rate and time. Group differences in brain metabolites and fMRI activation between ME/CFS and HCs were compared and correlated with behavioral and symptom severity measurements.

Results: The completion rate was 100% regardless of participant group without causing immediate fatigue. ME/CFS appeared to show a higher N-Acetylaspartate in L-DLPFC compared to HCs (OR = 8.49, p = 0.040), correlating with poorer fatigue, pain, and sleep quality scores (p‘s = 0.001-0.015). An increase in brain activation involving the frontal lobe and the brainstem was observed in ME/CFS compared to HCs (Z > 3.4, p‘s < 0.010).

Conclusions: The study demonstrates the feasibility of combining MRS and fMRI to capture neurochemical and neurophysiological features of ME/CFS in female participants. Further research with larger cohorts of more representative sampling and follow-ups is needed to validate these apparent differences between ME/CFS and HCs.

Source: Kaur R, Greeley B, Ciok A, Mehta K, Tsai M, Robertson H, Debelic K, Zhang LX, Nelson T, Boulter T, Siu W, Nacul L, Song X. A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation. Medicina (Kaunas). 2024 Aug 22;60(8):1370. doi: 10.3390/medicina60081370. PMID: 39202651. https://www.mdpi.com/1648-9144/60/8/1370 (Full text)

Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects

Abstract:

Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them.

To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by ACE III screening test (Overall Cognitive level – OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01).

We observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus.

In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients’ cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency.

This study shows that patients with neurological Long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Source: Serrano Del Pueblo VM, Serrano-Heras G, Romero Sánchez CM, Piqueras Landete P, Rojas-Bartolome L, Feria I, Morris RGM, Strange B, Mansilla F, Zhang L, Castro-Robles B, Arias-Salazar L, López-López S, Payá M, Segura T, Muñoz-López M. Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects. Brain. 2024 Apr 2:awae101. doi: 10.1093/brain/awae101. Epub ahead of print. PMID: 38562097. https://pubmed.ncbi.nlm.nih.gov/38562097/

Preferential Impairment of Auditory Working Memory in Long COVID: An Observational Study of Undergraduate Medical Students

Abstract:

Background: Long COVID is a multisystem condition with prolonged symptoms that develop after recovery from the COVID-19 infection, often following a mild infection. Few studies have been conducted on cognitive function among medical students after recovery from mild COVID-19. This study aimed to assess the attention span and working memory (WM) capacity of medical students after six months of recovery.

Methods: A cross-sectional study was performed on 17 young adult medical students who had suffered a mild COVID-19 infection at least six months prior. Eighteen age-matched healthy medical students served as the controls. Audio-visual WM tasks and attention spans were assessed using computerized software for both the cases and controls.

Results: The mean ages of the case and control were 19.67±1.6 and 20.0±1.2 years, respectively. The most common symptoms among cases were fatigue (33%), weight loss (26%), and nasal stuffiness (13%). The overall proportion of correct responses across all visual and auditory WM tasks (p=0.085) and reaction times (p=0.609) did not differ between the cases and controls. However, the overall target hit rate of the auditory WM task was significantly lower in cases than in controls (p=0.002). This difference was not observed in the visual WM task (p=0.374).

Conclusion: In the current study, the overall WM functions (visual and auditory combined) and attention span did not differ between cases and controls. However, auditory WM performance was significantly impaired in patients compared with controls, indicating selective impairment of auditory WM in patients with long COVID.

Source: Manna S, Ghosh Dastidar S, S R, et al. (January 01, 2024) Preferential Impairment of Auditory Working Memory in Long COVID: An Observational Study of Undergraduate Medical Students. Cureus 16(1): e51457. doi:10.7759/cureus.51457 https://www.cureus.com/articles/217296-preferential-impairment-of-auditory-working-memory-in-long-covid-an-observational-study-of-undergraduate-medical-students#!/ (Full text)

Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study

Abstract:

The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national longitudinal study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls.

Cognitive deficits were global and associated with elevated brain injury markers and reduced anterior cingulate cortex volume one year after admission. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Treatment with corticosteroids during the acute phase appeared protective against cognitive deficits. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 is immune-mediated, and should guide the development of therapeutic strategies.

Source: Benedict Michael, Greta Wood, Brendan Sargent et al. Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study, 05 January 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3818580/v1] https://www.researchsquare.com/article/rs-3818580/v1 (Full text)

Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation

Abstract:

The long-term effects of COVID-19 on cognitive function have become an area of increasing concern. This paper provides an overview of characteristics, risk factors, possible mechanisms, and management strategies for cognitive dysfunction in post-COVID-19 condition (PCC).

Prolonged cognitive dysfunction is one of the most common impairments in PCC, affecting between 17% and 28% of the individuals more than 12 weeks after the infection and persisting in some cases for several years. Cognitive dysfunctions can be manifested as a wide range of symptoms including memory impairment, attention deficit, executive dysfunction, and reduced processing speed. Risk factors for developing PCC, with or without cognitive impairments, include advanced age, preexisting medical conditions, and the severity of acute illness. The underlying mechanisms remain unclear, but proposed contributors include neuroinflammation, hypoxia, vascular damage, and latent virus reactivation not excluding the possibility of direct viral invasion of the central nervous system, illustrating complex viral pathology.

As the individual variation of the cognitive impairments is large, a neuropsychological examination and a person-centered multidimensional approach are required. According to the World Health Organization, limited evidence on COVID-19-related cognitive impairments necessitates implementing rehabilitation interventions from established practices of similar conditions. Psychoeducation and compensatory skills training are recommended. Assistive products and environmental modifications adapted to individual needs might be helpful. In specific attention- and working memory dysfunctions, cognitive training—carefully monitored for intensity—might be effective for people who do not suffer from post-exertional malaise. Further research is crucial for evidence-based interventions specific to COVID-19-related cognitive impairments.

Source: Möller M, Borg K, Janson C, Lerm M, Normark J, Niward K. Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation. J Intern Med. 2023 Sep 27. doi: 10.1111/joim.13720. Epub ahead of print. PMID: 37766515. https://onlinelibrary.wiley.com/doi/10.1111/joim.13720 (Full text)

Neuropsychological measures of post-COVID-19 cognitive status

Abstract:

Background: COVID-19 may result in persistent symptoms in the post-acute phase, including cognitive and neurological ones. The aim of this study is to investigate the cognitive and neurological features of patients with a confirmed diagnosis of COVID-19 evaluated in the post-acute phase through a direct neuropsychological evaluation.

Methods: Individuals recovering from COVID-19 were assessed in an out-patient practice with a complete neurological evaluation and neuropsychological tests (Mini-Mental State Examination; Rey Auditory Verbal Test, Multiple Feature Target Cancellation Test, Trial Making Test, Digit Span Forward and Backward, and Frontal Assessment Battery). Pre- and post-COVID-19 global and mental health status was assessed along with the history of the acute phase of infection. Post-COVID-19 cognitive status was modeled by combining persistent self-reported COVID-related cognitive symptoms and pathologic neuropsychological tests.

Results: A total of 406 individuals (average age 54.5 ± 15.1 years, 45.1% women) were assessed on average at 97.8 ± 48.0 days since symptom onset. Persistent self-reported neurological symptoms were found in the areas of sleep (32%), attention (31%), and memory (22%). The MMSE mean score was 28.6. In total, 84 subjects (20.7%) achieved pathologic neuropsychological test results. A high prevalence of failed tests was found in digit span backward (18.7%), trail making (26.6%), and frontal assessment battery (10.9%). Cognitive status was associated with a number of factors including cardiovascular disease history, persistent fatigue, female sex, age, anxiety, and mental health stress.

Conclusion: COVID-19 is capable of eliciting persistent measurable neurocognitive alterations particularly relevant in the areas of attention and working memory. These neurocognitive disorders have been associated with some potentially treatable factors and others that may stratify risk at an early stage.

Source: Lauria A, Carfì A, Benvenuto F, Bramato G, Ciciarello F, Rocchi S, Rota E, Salerno A, Stella L, Tritto M, Di Paola A, Pais C, Tosato M, Janiri D, Sani G, Lo Monaco R, Pagano FC, Fantoni M, Bernabei R, Landi F, Bizzarro A; Gemelli Against COVID-19 Post-acute Care Group. Neuropsychological measures of post-COVID-19 cognitive status. Front Psychol. 2023 Jul 10;14:1136667. doi: 10.3389/fpsyg.2023.1136667. PMID: 37492442; PMCID: PMC10363721. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363721/ (Full text)

Neurologic manifestations of long COVID differ based on acute COVID-19 severity

Abstract:

Objective: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients.

Methods: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021.

Results: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were “brain fog” (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients.

Interpretation: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions.

Source: Perez Giraldo GS, Ali ST, Kang AK, Patel TR, Budhiraja S, Gaelen JI, Lank GK, Clark JR, Mukherjee S, Singer T, Venkatesh A, Orban ZS, Lim PH, Jimenez M, Miller J, Taylor C, Szymanski AL, Scarpelli J, Graham EL, Balabanov RD, Barcelo BE, Cahan JG, Ruckman K, Shepard AG, Slutzky MW, LaFaver K, Kumthekar PU, Shetty NK, Carroll KS, Ho SU, Lukas RV, Batra A, Liotta EM, Koralnik IJ. Neurologic manifestations of long COVID differ based on acute COVID-19 severity. Ann Neurol. 2023 Mar 26. doi: 10.1002/ana.26649. Epub ahead of print. PMID: 36966460. https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.26649 (Full text available as PDF file)

 

Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life

Abstract:

Background: A considerable proportion of people experience lingering symptoms after Coronavirus Disease 2019 (COVID-19). The aim of this study was to investigate the frequency, pattern and functional implications of cognitive impairments in patients at a long-COVID clinic who were referred after hospitalisation with COVID-19 or by their general practitioner.

Methods: Patients underwent cognitive screening and completed questionnaires regarding subjective cognition, work function and quality of life. Patients’ cognitive performance was compared with that of 150 age-, sex-, and education-matched healthy controls (HC) and with their individually expected performance calculated based on their age, sex and education.

Results: In total, 194 patients were assessed, on average 7 months (standard deviation: 4) after acute COVID-19.44-53 % of the patients displayed clinically relevant cognitive impairments compared to HC and to their expected performance, respectively. Moderate to large impairments were seen in global cognition and in working memory and executive function, while mild to moderate impairments occurred in verbal fluency, verbal learning and memory. Hospitalised (n = 91) and non-hospitalised (n = 103) patients showed similar degree of cognitive impairments in analyses adjusted for age and time since illness. Patients in the cognitively impaired group were older, more often hospitalised, had a higher BMI and more frequent asthma, and were more often female. More objective cognitive impairment was associated with more subjective cognitive difficulties, poorer work function and lower quality of life.

Limitations: The study was cross-sectional, which precludes causality inferences.

Conclusions: These findings underscore the need to assess and treat cognitive impairments in patients at long-COVID clinics.

Source: Miskowiak KW, Pedersen JK, Gunnarsson DV, Roikjer TK, Podlekareva D, Hansen H, Dall CH, Johnsen S. Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life. J Affect Disord. 2022 Dec 28;324:162-169. doi: 10.1016/j.jad.2022.12.122. Epub ahead of print. PMID: 36586593; PMCID: PMC9795797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795797/ (Full text)

Investigating the neural substrates of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) : a structural and functional MRI study

Abstract:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterised by continuous fatigue and has many diagnostic criteria. Cognitive dysfunction affects 86-94% of adults with CFS/ME.

This thesis used MRI applications to investigate brain structure and function in CFS/ME. This thesis hypothesised to find brain volume differences, functional connectivity differences in brain networks, and functional differences measured by Blood Oxygenation Level Dependant (BOLD) signal activation during working memory task performance.

The working memory paradigm was designed to investigate working memory components, processing and storage separately and combined. The relationship between fatigue and performance was assessed. This thesis’s original contribution provides evidence that the salience network might have altered resting-state functional connectivity in CFS/ME in the absence of morphological differences.

The salience network is involved in detecting and integrating salient sensory information; therefore, disruption in this network might disrupt incoming cognitive stimuli and influence other networks’ connectivity, involved in fatigue and impaired memory.

In the more demanding task, participants with CFS/ME were slower and less accurate but used the same working memory network as healthy controls. No brain volume differences, nor atrophy were found. The differences between these findings compared to previous studies might be due to different study designs, analysis methods, sample sizes with different symptoms, including illness duration, physical inactivity and sleep disturbance.

The salience network alteration could potentially have a significant role in CFS/ME, as we cannot determine cause and effect with current experimental design the association with fatigue and other CFS/ME symptoms remains unclear. Using longitudinal studies that account for neurologically relevant confounders are needed in CFS/ME to further investigate the role of salience network.

Source: Almutairi, Basim S. Investigating the neural substrates of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) : a structural and functional MRI study. PhD Thesis, University of Bristol. uk.bl.ethos.866683  https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.866683

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)