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      Cognitive decline in post-COVID-19 syndrome does not correspond with persisting neuronal or astrocytic damage

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          Abstract

          Cognitive impairment is the most frequent symptom reported in post-COVID-19 syndrome (PCS). Aetiology of cognitive impairment in PCS is still to be determined. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are increased in acute COVID-19. Their role as biomarkers in other neurological disorders is under debate. We analysed serum levels of NfL and GFAP as markers for neuronal and astrocytic damage in 53 patients presenting to a PCS Neurology outpatient clinic. Only individuals with self-reported cognitive complaints were included. In these individuals, cognitive complaints were further assessed by comprehensive neuropsychological assessment (NPA). Patients were categorized into subgroups of subjective cognitive decline, single domain impairment, or multi-domain impairment. Serum NfL was in normal range, however an increase of serum GFAP was detected in 4% of patients. Serum NfL and GFAP levels correlated with each other, even when adjusting for patient age (r = 0.347, p = 0.012). NPA showed deficits in 70%; 40% showing impairment in several tested domains. No significant differences were found between serum NfL- and GFAP-levels comparing patients with subjective cognitive decline, single domain impairment, or multi-domain impairment. Persistent neuronal or astrocytic damage did not correlate with cognitive impairment in PCS.

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          Most cited references40

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          The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

          To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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            A minimal common outcome measure set for COVID-19 clinical research

            Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.
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              A clinical case definition of post-COVID-19 condition by a Delphi consensus

              People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.
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                Author and article information

                Contributors
                fabian.boesl@charite.de
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                4 March 2024
                4 March 2024
                2024
                : 14
                : 5326
                Affiliations
                [1 ]Department of Neurology, Charité-University Medicine Berlin, Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, ( https://ror.org/01hcx6992) Hindenburgdamm 30, 12203 Berlin, Germany
                [2 ]GRID grid.6190.e, ISNI 0000 0000 8580 3777, Department of Neurology, Faculty of Medicine and University Hospital Cologne, , University of Cologne, ; Cologne, Germany
                [3 ]GRID grid.6190.e, ISNI 0000 0000 8580 3777, Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, , University of Cologne, ; Cologne, Germany
                [4 ]GRID grid.410607.4, Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), , University Medical Center of the Johannes Gutenberg University Mainz, ; Rhine-Main Neuroscience Network (rmn2), Mainz, Germany
                Author information
                http://orcid.org/0000-0002-7345-7701
                http://orcid.org/0000-0002-7665-1171
                Article
                55881
                10.1038/s41598-024-55881-1
                10912552
                38438479
                a93916e3-4758-4b90-a324-ddf3b5446d33
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 August 2023
                : 27 February 2024
                Funding
                Funded by: FundRef 501100001659, Deutsche Forschungsgemeinschaft (German Research Foundation);
                Award ID: FR 4479/1-1
                Award ID: WA 4101/2-1
                Funded by: Charité - Universitätsmedizin Berlin (3093)
                Categories
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                © Springer Nature Limited 2024

                Uncategorized
                neurological disorders,biomarkers
                Uncategorized
                neurological disorders, biomarkers

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