{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:49:11Z","timestamp":1790804951908,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age &amp;gt; 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and\/or olfaction, performance &amp;lt; 26 points on a Montreal Cognitive Assessment and\/or pathological findings on clinical neurological examination). Patients with \u22652 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 \u00b1 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29\/29 and 25\/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18\/26 patients (mean score 21.8\/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10\/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.<\/jats:p>","DOI":"10.1093\/brain\/awab009","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T20:23:55Z","timestamp":1611001435000},"page":"1263-1276","source":"Crossref","is-referenced-by-count":343,"title":["Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7696-9334","authenticated-orcid":false,"given":"Jonas A","family":"Hosp","sequence":"first","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1415-1929","authenticated-orcid":false,"given":"Andrea","family":"Dressing","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"},{"name":"Freiburg Brain Imaging Center, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-7373","authenticated-orcid":false,"given":"Ganna","family":"Blazhenets","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bormann","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5881-6043","authenticated-orcid":false,"given":"Alexander","family":"Rau","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Schwabenland","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Thurow","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Wagner","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine II, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5777-0212","authenticated-orcid":false,"given":"Cornelius","family":"Waller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf D","family":"Niesen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-8935","authenticated-orcid":false,"given":"Lars","family":"Frings","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Urbach","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0349-1955","authenticated-orcid":false,"given":"Marco","family":"Prinz","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany"},{"name":"Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany"},{"name":"Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-5714","authenticated-orcid":false,"given":"Cornelius","family":"Weiller","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"},{"name":"Freiburg Brain Imaging Center, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3833-9822","authenticated-orcid":false,"given":"Nils","family":"Schroeter","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp T","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,3]]},"reference":[{"key":"2021070801274571500_awab009-B1","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1093\/brain\/awaa240","article-title":"The emerging spectrum of COVID-19 neurology: Clinical, radiological and laboratory findings","volume":"143","author":"Paterson","year":"2020","journal-title":"Brain."},{"key":"2021070801274571500_awab009-B2","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1001\/jamaneurol.2020.2065","article-title":"Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019: A review","volume":"77","author":"Zubair","year":"2020","journal-title":"JAMA Neurol."},{"key":"2021070801274571500_awab009-B3","author":"Mao"},{"key":"2021070801274571500_awab009-B4","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1056\/NEJMc2008597","article-title":"Neurologic features in severe SARS-CoV-2 infection","volume":"382","author":"Helms","year":"2020","journal-title":"N Engl J Med."},{"key":"2021070801274571500_awab009-B5","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1007\/s00415-020-10050-y","article-title":"Association of neuronal injury blood marker neurofilament light chain with mild-to-moderate COVID-19","volume":"267","author":"Ameres","year":"2020","journal-title":"J Neurol"},{"key":"2021070801274571500_awab009-B6","doi-asserted-by":"crossref","first-page":"e1754","DOI":"10.1212\/WNL.0000000000010111","article-title":"Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19","volume":"95","author":"Kanberg","year":"2020","journal-title":"Neurology."},{"key":"2021070801274571500_awab009-B7","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3390\/jcm9030703","article-title":"Sepsis-associated encephalopathy: From delirium to dementia?","volume":"9","author":"Chung","year":"2020","journal-title":"J Clin Med"},{"key":"2021070801274571500_awab009-B8","doi-asserted-by":"crossref","first-page":"h2538","DOI":"10.1136\/bmj.h2538","article-title":"Outcome of delirium in critically ill patients: Systematic review and meta-analysis","volume":"350","author":"Salluh","year":"2015","journal-title":"BMJ."},{"key":"2021070801274571500_awab009-B9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bbi.2020.04.027","article-title":"Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms","volume":"87","author":"Troyer","year":"2020","journal-title":"Brain Behav Immun."},{"key":"2021070801274571500_awab009-B10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/v12010014","article-title":"Human coronaviruses and other respiratory viruses: Underestimated opportunistic pathogens of the central nervous system?","volume":"12","author":"Desforges","year":"2019","journal-title":"Viruses"},{"key":"2021070801274571500_awab009-B11","doi-asserted-by":"crossref","first-page":"e00404-18","DOI":"10.1128\/JVI.00404-18","article-title":"Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43","volume":"92","author":"Dub\u00e9","year":"2018","journal-title":"J Virol."},{"key":"2021070801274571500_awab009-B12","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/jmv.25728","article-title":"The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients","volume":"92","author":"Li","year":"2020","journal-title":"J Med Virol."},{"key":"2021070801274571500_awab009-B13","first-page":"26:1426-1427","article-title":"Anosmia in COVID-19 patients","author":"Hornuss","year":"2020","journal-title":"Clin Microbiol Infect."},{"key":"2021070801274571500_awab009-B14","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00405-020-05965-1","article-title":"Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study [Internet","volume":"277","author":"Lechien","year":"2020","journal-title":"Eur Arch Otorhinolaryngol."},{"key":"2021070801274571500_awab009-B15","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/jmv.20255","article-title":"An interferon-?-related cytokine storm in SARS patients","volume":"75","author":"Huang","year":"2005","journal-title":"J Med Virol."},{"key":"2021070801274571500_awab009-B16","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1126\/science.1114332","article-title":"Mapping of functional neural pathways by autoradiographic survey of local metabolic rate with (14C)deoxyglucose","volume":"187","author":"Kennedy","year":"1975","journal-title":"Science."},{"key":"2021070801274571500_awab009-B17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"2021070801274571500_awab009-B18","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","article-title":"A clinical approach to diagnosis of autoimmune encephalitis","volume":"15","author":"Graus","year":"2016","journal-title":"Lancet Neurol."},{"key":"2021070801274571500_awab009-B19","first-page":"222","article-title":"\u2018Sniffin\u2019 sticks\u2019: Screening of olfactory performance","volume":"34","author":"Kobal","year":"1996","journal-title":"Rhinology."},{"key":"2021070801274571500_awab009-B20","author":"H\u00fcttenbrink"},{"key":"2021070801274571500_awab009-B21","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal cognitive assessment, MoCA: A brief screening tool for mild cognitive impairment: MOCA: A BRIEF screening tool for MCI","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc."},{"key":"2021070801274571500_awab009-B22","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.jcin.2017.10.041","article-title":"Neurocognition and cerebral lesion burden in high-risk patients before undergoing transcatheter aortic valve replacement","volume":"11","author":"Lazar","year":"2018","journal-title":"JACC Cardiovasc Interv."},{"key":"2021070801274571500_awab009-B23","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1007\/s00259-009-1264-0","article-title":"EANM procedure guidelines for PET brain imaging using [18F]FDG, version 2","volume":"36","author":"Varrone","year":"2009","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"2021070801274571500_awab009-B24","doi-asserted-by":"crossref","first-page":"418","DOI":"10.2967\/jnumed.119.231407","article-title":"18F-FDG PET imaging of the inferior colliculus in asymmetric hearing loss","volume":"61","author":"Speck","year":"2020","journal-title":"J Nucl Med"},{"key":"2021070801274571500_awab009-B25","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.tins.2009.06.003","article-title":"Metabolic brain networks in neurodegenerative disorders: A functional imaging approach","volume":"32","author":"Eidelberg","year":"2009","journal-title":"Trends Neurosci."},{"key":"2021070801274571500_awab009-B26","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2967\/jnumed.118.219097","article-title":"Principal components analysis of brain metabolism predicts development of Alzheimer dementia","volume":"60","author":"Blazhenets","year":"2019","journal-title":"J Nucl Med"},{"key":"2021070801274571500_awab009-B27","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1016\/j.neuroimage.2010.10.025","article-title":"Scaled subprofile modeling of resting state imaging data in Parkinson\u2019s disease: Methodological issues","volume":"54","author":"Spetsieris","year":"2011","journal-title":"NeuroImage."},{"key":"2021070801274571500_awab009-B28","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nn.4475","article-title":"The role of peripheral immune cells in the CNS in steady state and disease","volume":"20","author":"Prinz","year":"2017","journal-title":"Nat Neurosci."},{"key":"2021070801274571500_awab009-B29","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1111\/ene.14382","article-title":"A systematic review of neurological manifestations of SARS-CoV-2 infection: The devil is hidden in the details","volume":"27","author":"Romoli","year":"2020","journal-title":"Eur J Neurol."},{"key":"2021070801274571500_awab009-B30","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1513\/AnnalsATS.201804-233OC","article-title":"Preliminary validation of the montreal cognitive assessment tool among sepsis survivors: A prospective pilot study","volume":"15","author":"Brown","year":"2018","journal-title":"Ann Am Thorac Soc"},{"key":"2021070801274571500_awab009-B31","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.aucc.2017.06.001","article-title":"Post-sepsis cognitive impairment and associated risk factors: A systematic review","volume":"31","author":"Calsavara","year":"2018","journal-title":"Aust Crit Care."},{"key":"2021070801274571500_awab009-B32","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-3-319-44775-9_7","volume-title":"Cognitive screening instruments","author":"Julayanont","year":"2017"},{"key":"2021070801274571500_awab009-B33","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMc2019373","article-title":"Neuropathological features of Covid-19","volume":"383","author":"Solomon","year":"2020","journal-title":"N Engl J Med."},{"key":"2021070801274571500_awab009-B34","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s11239-020-02230-4","article-title":"COVID-19-associated vasculitis and vasculopathy","volume":"50","author":"Becker","year":"2020","journal-title":"J Thromb Thrombolysis."},{"key":"2021070801274571500_awab009-B35","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet."},{"key":"2021070801274571500_awab009-B36","author":"Song"},{"key":"2021070801274571500_awab009-B37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1742-2094-5-38","article-title":"Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism","volume":"5","author":"Semmler","year":"2008","journal-title":"J Neuroinflammation."},{"key":"2021070801274571500_awab009-B38","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1177\/0271678X17701764","article-title":"2-18F-fluoro-2-deoxyglucose positron emission tomography in delirium","volume":"37","author":"Haggstrom","year":"2017","journal-title":"J Cereb Blood Flow Metab"},{"key":"2021070801274571500_awab009-B39","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/path.1560","article-title":"Organ distribution of severe acute respiratory syndrome(SARS) associated coronavirus(SARS-CoV) in SARS patients: Implications for pathogenesis and virus transmission pathways","volume":"203","author":"Ding","year":"2004","journal-title":"J Pathol."},{"key":"2021070801274571500_awab009-B40","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1016\/S2666-5247(20)30004-5","article-title":"Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: An observational study","volume":"1","author":"Chu","year":"2020","journal-title":"Lancet Microbe."},{"key":"2021070801274571500_awab009-B41","doi-asserted-by":"crossref","first-page":"eabc5801","DOI":"10.1126\/sciadv.abc5801","article-title":"Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia","volume":"6","author":"Brann","year":"2020","journal-title":"Sci Adv."},{"issue":"2","key":"2021070801274571500_awab009-B42","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/ana.25783","article-title":"Steroid-Responsive Encephalitis in Coronavirus Disease 2019","volume":"88","author":"Pilotto","year":"2020","journal-title":"Annals of Neurology"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awab009\/37001329\/awab009.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/144\/4\/1263\/37903321\/awab009.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/144\/4\/1263\/37903321\/awab009.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T03:53:37Z","timestamp":1625716417000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/144\/4\/1263\/6209743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,1]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,3]]},"published-print":{"date-parts":[[2021,5,7]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awab009","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,4,1]]},"published":{"date-parts":[[2021,4,1]]}}}