Tag: executive function

Reduced Cortical Thickness Correlates of Cognitive Dysfunction in Post-COVID-19 Condition: Insights from a Long-Term Follow-up

Abstract:

Background and purpose: There is a paucity of data on long-term neuroimaging findings from individuals who have developed the post-coronavirus 2019 (COVID-19) condition. Only 2 studies have investigated the correlations between cognitive assessment results and structural MR imaging in this population. This study aimed to elucidate the long-term cognitive outcomes of participants with the post-COVID-19 condition and to correlate these cognitive findings with structural MR imaging data in the post-COVID-19 condition.

Materials and methods: A cohort of 53 participants with the post-COVID-19 condition underwent 3T brain MR imaging with T1 and FLAIR sequences obtained a median of 1.8 years after Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. A comprehensive neuropsychological battery was used to assess several cognitive domains in the same individuals. Correlations between cognitive domains and whole-brain voxel-based morphometry were performed. Different ROIs from FreeSurfer were used to perform the same correlations with other neuroimaging features.

Results: According to the Frascati criteria, more than one-half of the participants had deficits in the attentional (55%, n = 29) and executive (59%, n = 31) domains, while 40% (n = 21) had impairment in the memory domain. Only 1 participant (1.89%) showed problems in the visuospatial and visuoconstructive domains. We observed that reduced cortical thickness in the left parahippocampal region (t(48) = 2.28, P = .03) and the right caudal-middle-frontal region (t(48) = 2.20, P = .03) was positively correlated with the memory domain.

Conclusions: Our findings suggest that cognitive impairment in individuals with the post-COVID-19 condition is associated with long-term alterations in the structure of the brain. These macrostructural changes may provide insight into the nature of cognitive symptoms.

Source: Dacosta-Aguayo R, Puig J, Lamonja-Vicente N, Carmona-Cervelló M, Biaani León-Gómez B, Monté-Rubio G, López-Linfante VM, Zamora-Putin V, Montero-Alia P, Chacon C, Bielsa J, Moreno-Gabriel E, Garcia-Sierra R, Pachón A, Costa A, Mataró M, Prado JG, Martinez-Cáceres E, Mateu L, Massanella M, Violán C, Torán-Monserrat P; Aliança ProHEpiC-19 Cognitiu (The APC Collaborative Group). Reduced Cortical Thickness Correlates of Cognitive Dysfunction in Post-COVID-19 Condition: Insights from a Long-Term Follow-up. AJNR Am J Neuroradiol. 2024 Apr 4. doi: 10.3174/ajnr.A8167. Epub ahead of print. PMID: 38575319. https://pubmed.ncbi.nlm.nih.gov/38575319/

SARS-CoV2 evokes structural brain changes resulting in declined executive function

Abstract:

Background: Several research has underlined the multi-system character of COVID-19. Though effects on the Central Nervous System are mainly discussed as disease-specific affections due to the virus’ neurotropism, no comprehensive disease model of COVID-19 exists on a neurofunctional base by now. We aimed to investigate neuroplastic grey- and white matter changes related to COVID-19 and to link these changes to neurocognitive testings leading towards a multi-dimensional disease model.

Methods: Groups of acutely ill COVID-19 patients (n = 16), recovered COVID-19 patients (n = 21) and healthy controls (n = 13) were prospectively included into this study. MR-imaging included T1-weighted sequences for analysis of grey matter using voxel-based morphometry and diffusion-weighted sequences to investigate white matter tracts using probabilistic tractography. Comprehensive neurocognitive testing for verbal and non-verbal domains was performed.

Results: Alterations strongly focused on grey matter of the frontal-basal ganglia-thalamus network and temporal areas, as well as fiber tracts connecting these areas. In acute COVID-19 patients, a decline of grey matter volume was found with an accompanying diminution of white matter tracts. A decline in executive function and especially verbal fluency was found in acute patients, partially persisting in recovered.

Conclusion: Changes in gray matter volume and white matter tracts included mainly areas involved in networks of executive control and language. Deeper understanding of these alterations is necessary especially with respect to long-term impairments, often referred to as ‘Post-COVID’.

Source: Deuter D, Hense K, Kunkel K, Vollmayr J, Schachinger S, Wendl C, Schicho A, Fellner C, Salzberger B, Hitzenbichler F, Zeller J, Vielsmeier V, Dodoo-Schittko F, Schmidt NO, Rosengarth K. SARS-CoV2 evokes structural brain changes resulting in declined executive function. PLoS One. 2024 Mar 12;19(3):e0298837. doi: 10.1371/journal.pone.0298837. PMID: 38470899; PMCID: PMC10931481. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10931481/ (Full text)

Cognition and Memory after Covid-19 in a Large Community Sample

Abstract:

Background: Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods: We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (“brain fog”).

Results: Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions: Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).

Source: Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P. Cognition and Memory after Covid-19 in a Large Community Sample. N Engl J Med. 2024 Feb 29;390(9):806-818. doi: 10.1056/NEJMoa2311330. PMID: 38416429. https://www.nejm.org/doi/10.1056/NEJMoa2311330 (Full text)

Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection

Abstract:

Introduction: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID.

Case presentation: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region.

Conclusion: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.

Source: Benis D, Voruz P, Chiuve SC, Garibotto V, Assal F, Krack P, Péron J, Fleury V. Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection. Case Rep Neurol. 2023 Dec 5;16(1):6-17. doi: 10.1159/000535241. PMID: 38179211; PMCID: PMC10764086. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764086/ (Full text)

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)

From ‘mental fog’ to post-acute COVID-19 syndrome’s executive function alteration: Implications for clinical approach

Abstract:

A common symptom of the neuropsychiatric Post-Acute COVID-19 syndrome (neuro-PACS) is the so called ‘brain fog’. Patients describe the brain fog as problems with attention, memory and mental fatigue. Brain fog is experienced by 9-55% of people for months after having contracted SARS-CoV-2 virus. Several theories have been proposed to explain PACS’s brain fog, including a neuroinflammatory hypothesis, but the hypothesis remains to be proven. Here, we examined inflammatory and immunological blood profile in a cohort of patients with PACS to investigate the association between executive functions and blood inflammatory markers.

Executive function was assessed by the Trail Making Test (TMT) Part A and Part B, as well as the Barkley Deficits in Executive Functioning Scale (BDEFS), in 71 patients (36 men), average age of 40 years (range: 15-82, SD: 15.7). Impairment in executive functioning (BDEFS scores and TMT B scores) correlated with increased levels of Interleukin-6 (IL-6), fibrinogen and ferritin. Moreover, elevated levels of Il-6, fibrinogen, ferritin, tumor necrosis factor-alpha and C-reactive protein have been observed in PACS.

These findings demonstrate that PACS is characterized by the presence of an immuno-inflammatory process, which is associated with diminished executive functioning. Here, we argue in favour of a shift from the non-descriptive definition of ‘mental fog’ to a characterization of a subtype of PACS, associated with alteration in executive functioning. Implication for clinical settings and prevention are discussed.

Source: Pallanti S, Di Ponzio M, Gavazzi G, Gasic G, Besteher B, Heller C, Kikinis R, Makris N, Kikinis Z. From ‘mental fog’ to post-acute COVID-19 syndrome’s executive function alteration: Implications for clinical approach. J Psychiatr Res. 2023 Sep 30;167:10-15. doi: 10.1016/j.jpsychires.2023.09.017. Epub ahead of print. PMID: 37804756. https://pubmed.ncbi.nlm.nih.gov/37804756/

Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study)

Abstract:

Purpose: Approximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired during sitting and active standing in 30 patients with PoTS compared with 30 healthy controls (HCs) and whether it will improve with the counter manoeuvre of leg crossing.

Methods: In this prospective pilot study, patients with PoTS were compared to HCs matched for age, sex, and educational level. Baseline data included norepinephrine plasma levels, autonomic testing and baseline cognitive function in a seated position [the Montreal Cognitive Assessment, the Leistungsprüfsystem (LPS) subtests 1 and 2, and the Test of Attentional Performance (TAP)]. Cognitive functioning was examined in a randomized order in supine, upright and upright legs crossed position. The primary outcomes were the cognitive test scores between HCs and patients with PoTS at baseline testing, and among the different body positions.

Results: Patients with PoTS had impaired attention (TAP median reaction time) in the seated position and impaired executive functioning (Stroop) while standing compared with HC. Stroop was influenced by position (supine versus upright versus upright legs crossed) only in the PoTS group. Leg crossing did not result in an improvement in executive function. In patients with PoTS, there was a negative correlation of Stroop with norepinephrine plasma levels while standing.

Conclusion: Compared with HCs, PoTS participants showed impaired cognitive attention and executive function in the upright position that did not improve in the legs crossed position. Data provide further evidence for orthostatic cognitive deterioration in patients with PoTS.

Trial Registration Information: The study was registered at ClinicalTrials.gov (NCT03681080).

Source: Maier, A., Schopen, L., Thiel, J.C. et al. Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study). Clin Auton Res (2023). https://doi.org/10.1007/s10286-023-00950-0 https://link.springer.com/article/10.1007/s10286-023-00950-0 (Full text)

COVID-19 and Cognitive Function: Evidence for Increased Processing Speed Variability in COVID-19 Survivors and Multifaceted Impairment with LongCOVID Symptoms

Abstract:

Background: There is increasing evidence for cognitive function to be negatively impacted by COVID-19. There is, however, limited research evaluating cognitive function pre- and postCOVID-19 using objective measures.

Methods: We examined processing speed, attention, working memory, executive function and memory in adults (≤69 years) with a history of COVID-19 (n=129; assessed ≥20 days after diagnosis, none acutely unwell), compared to those with no known history of COVID-19 (n=93). We also examined cognitive changes in a sub-group of COVID (n=30) and non-COVID (n=33) participants, compared to their pre-COVID-19 pandemic level (data available through the MyCognition database).

Results: Cross-sectionally, the COVID group showed significantly larger intra-individual variability in processing speed, compared to the non-COVID group. The COVID sub-group also showed significantly larger intra-individual variability in processing speed, compared to their
pre-COVID level; no significant change occurred in non-COVID participants over the same time scale. Other cognitive indices were not significantly impacted in the cross-sectional or withinsubjects investigations, but participants (n=20) who had needed hospitalisation due to COVID19 showed poor attention and executive function relative to those who had not required hospitalisation (n=109). Poor health and long-COVID symptoms  correlated with poor cognitive function across domains in the COVID group.

Conclusions: The findings indicate a limited cognitive impact of COVID-19 with only intraindividual variability in processing speed being significantly impacted in an adult UK sample. However, those who required hospitalisation due to COVID-19 severity and/or experience long-COVID symptoms display multifaceted cognitive impairment and may benefit from repeated cognitive assessments and remediation efforts.

Source: Vakani K, Ratto M, Sandford-James A, Antonova E, Kumari V. COVID-19 and Cognitive Function: Evidence for Increased Processing Speed Variability in COVID-19 Survivors and Multifaceted Impairment with Long-COVID Symptoms. Eur Psychiatry. 2023 May 12:1-34. doi: 10.1192/j.eurpsy.2023.25. Epub ahead of print. PMID: 37170616. https://www.cambridge.org/core/services/aop-cambridge-core/content/view/AE8EFA3BF7DC84334EEBC3039427801C/S0924933823000251a.pdf/covid-19-and-cognitive-function-evidence-for-increased-processing-speed-variability-in-covid-19-survivors-and-multifaceted-impairment-with-long-covid-symptoms.pdf (Full text available as PDF file)

Deficient GABABergic and glutamatergic excitability in the motor cortex of patients with long-COVID and cognitive impairment

Abstract:

Objective: Attention, working memory and executive processing have been reported to be consistently impaired in Neuro-Long coronavirus disease (COVID). On the hypothesis of abnormal cortical excitability, we investigated the functional state of inhibitory and excitatory cortical regulatory circuits by single “paired-pulse” transcranial magnetic stimulation (ppTMS) and Short-latency Afferent Inhibition (SAI).

Methods: We compared clinical and neurophysiological data of 18 Long COVID patients complaining of persistent cognitive impairment with 16 Healthy control (HC) subjects. Cognitive status was evaluated by means of the Montreal Cognitive Assessment (MoCA) and a neuropsychological evaluation of the executive function domain; fatigue was scored by the Fatigue Severity Scale (FSS). Resting motor threshold (RMT), the amplitude of the motor evoked potential (MEP), Short Intra-cortical Inhibition (SICI), Intra-cortical Facilitation (ICF), Long-interval Intracortical Inhibition (LICI) and Short-afferent inhibition (SAI) were investigated over the motor (M1) cortex.

Results: MoCA corrected scores were significantly different between the two groups (p = 0.023). The majority of the patients’ performed sub-optimally in the neuropsychological assessment of the executive functions. The majority (77.80%) of the patients reported high levels of perceived fatigue in the FSS. RMT, MEPs, SICI and SAI were not significantly different between the two groups. On the other hand, Long COVID patients showed a reduced amount of inhibition in LICI (p = 0.003) and a significant reduction in ICF (p < 0.001).

Conclusions: Neuro-Long COVID patients performing sub-optimally in the executive functions showed a reduction of LICI related to GABAb inhibition and a reduction of ICF related to glutamatergic regulation. No alteration in cholinergic circuits was found.

Significance: These findings can help to better understand the neurophysiological characteristics of Neuro-Long COVID, and in particular, motor cortex regulation in people with “brain fog”.

Source: Manganotti P, Michelutti M, Furlanis G, Deodato M, Buoite Stella A. Deficient GABABergic and glutamatergic excitability in the motor cortex of patients with long-COVID and cognitive impairment. Clin Neurophysiol. 2023 May 10;151:83-91. doi: 10.1016/j.clinph.2023.04.010. Epub ahead of print. PMID: 37210757; PMCID: PMC10170904. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170904/ (Full text)

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)