Assessment of Cognitive Function in Patients After COVID-19 Infection | Dementia and Cognitive Impairment | JAMA Network Open | JAMA Network
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Table 1.  Characteristics of Patients Who Had COVID-19
Characteristics of Patients Who Had COVID-19
Table 2.  Prevalence of Cognitive Impairment After COVID-19 Infection
Prevalence of Cognitive Impairment After COVID-19 Infection
1.
Alnefeesi  Y, Siegel  A, Lui  LMW,  et al.  Impact of SARS-CoV-2 infection on cognitive function: a systematic review.   Front Psychiatry. 2021;11:621773. doi:10.3389/fpsyt.2020.621773PubMedGoogle Scholar
2.
Weintraub  S, Besser  L, Dodge  HH,  et al.  Version 3 of the Alzheimer Disease Centers’ neuropsychological test battery in the Uniform Data Set (UDS).   Alzheimer Dis Assoc Disord. 2018;32(1):10-17. doi:10.1097/WAD.0000000000000223PubMedGoogle ScholarCrossref
3.
Benedict  RH, Schretlen  D, Groninger  L, Brandt  J.  Hopkins Verbal Learning Test–Revised: normative data and analysis of inter-form and test-retest reliability.   Clin Neuropsychol. 1998;12(1):43-55. doi:10.1076/clin.12.1.43.1726Google ScholarCrossref
4.
Helms  J, Kremer  S, Merdji  H,  et al.  Neurologic features in severe SARS-CoV-2 infection.   N Engl J Med. 2020;382(23):2268-2270. doi:10.1056/NEJMc2008597PubMedGoogle ScholarCrossref
5.
Pandharipande  PP, Girard  TD, Jackson  JC,  et al; BRAIN-ICU Study Investigators.  Long-term cognitive impairment after critical illness.   N Engl J Med. 2013;369(14):1306-1316. doi:10.1056/NEJMoa1301372PubMedGoogle ScholarCrossref
6.
Beraki  S, Aronsson  F, Karlsson  H, Ogren  SO, Kristensson  K.  Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice.   Mol Psychiatry. 2005;10(3):299-308. doi:10.1038/sj.mp.4001545PubMedGoogle ScholarCrossref
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    1 Comment for this article
    Vaccination status
    Chris Hasvold, BS | Non Medical
    When I saw this study referred to in a news source, the author stated that the patients either had COVID-19 OR were merely vaccinated. However, this study doesn't seem to indicate if the results were the same if the patient was COVID positive or only had been vaccinated. Can you clarify?
    CONFLICT OF INTEREST: None Reported
    Views 91,500
    Citations 0
    Research Letter
    Neurology
    October 22, 2021

    Assessment of Cognitive Function in Patients After COVID-19 Infection

    Author Affiliations
    • 1Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
    • 2Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York
    • 3The Catherine and Henry J. Gaisman Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
    JAMA Netw Open. 2021;4(10):e2130645. doi:10.1001/jamanetworkopen.2021.30645
    Introduction

    People who have survived COVID-19 frequently complain of cognitive dysfunction, which has been described as brain fog. The prevalence of post–COVID-19 cognitive impairment and the association with disease severity are not well characterized. Previous studies on the topic have been limited by small sample sizes and suboptimal measurement of cognitive functioning.1 We investigated rates of cognitive impairment in survivors of COVID-19 who were treated in outpatient, emergency department (ED), or inpatient hospital settings.

    Methods

    We analyzed data in this cross-sectional study from April 2020 through May 2021 from a cohort of patients with COVID-19 followed up through a Mount Sinai Health System registry. Study participants were 18 years or older, spoke English or Spanish, tested positive for SARS-CoV-2 or had serum antibody positivity, and had no history of dementia. Participant demographic characteristics (eg, age, race, and ethnicity) were collected via self-report. Cognitive functioning was assessed using well-validated neuropsychological measures: Number Span forward (attention) and backward (working memory), Trail Making Test Part A and Part B (processing speed and executive functioning, respectively), phonemic and category fluency (language), and the Hopkins Verbal Learning Test–Revised (memory encoding, recall, and recognition). The Mount Sinai Health System Institutional Review Board approved this study, and informed consent was obtained from study participants. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

    We calculated the frequency of impairment on each measure, defined as a z score of less than or equal to 1.5 SDs below measure-specific age-, educational level–, and sex-adjusted norms.2,3 Logistic regression assessed the association between cognitive impairment and COVID-19 care site (outpatient, ED, or hospital), adjusting for race and ethnicity, smoking, body mass index, comorbidities, and depression. The threshold for statistical significance was α = .05, and the tests were 2-tailed. Analyses were performed using SAS, version 9.4 (SAS Institute).

    Results

    The mean (IQR) age of 740 participants was 49 (38-59) years, 63% (n = 464) were women, and the mean (SD) time from COVID-19 diagnosis was 7.6 (2.7) months (Table 1). Participants self-identified as Black (15%), Hispanic (20%), or White (54%) or selected multiracial or other race and ethnicity (11%; other race included Asian [4.5%, n = 33)] and those who selected “other” as race). The most prominent deficits were in processing speed (18%, n = 133), executive functioning (16%, n = 118), phonemic fluency (15%, n = 111) and category fluency (20%, n = 148), memory encoding (24%, n = 178), and memory recall (23%, n = 170; Table 2).

    In adjusted analyses, hospitalized patients were more likely to have impairments in attention (odds ratio [OR]: 2.8; 95% CI: 1.3-5.9), executive functioning (OR: 1.8; 95% CI: 1.0-3.4), category fluency (OR: 3.0; 95% CI: 1.7-5.2), memory encoding (OR: 2.3; 95% CI: 1.3-4.1), and memory recall (OR: 2.2; 95% CI: 1.3-3.8) than those in the outpatient group. Patients treated in the ED were more likely to have impaired category fluency (OR: 1.8; 95% CI: 1.1-3.1) and memory encoding (OR: 1.7; 95% CI: 1.0-3.0) than those treated in the outpatient setting. No significant differences in impairments in other domains were observed between groups.

    Discussion

    In this study, we found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were predominant among hospitalized patients. The relative sparing of memory recognition in the context of impaired encoding and recall suggests an executive pattern. This pattern is consistent with early reports describing a dysexecutive syndrome after COVID-194 and has considerable implications for occupational, psychological, and functional outcomes. It is well known that certain populations (eg, older adults) may be particularly susceptible to cognitive impairment after critical illness5; however, in the relatively young cohort in the present study, a substantial proportion exhibited cognitive dysfunction several months after recovering from COVID-19. The findings of this study are generally consistent with those of research on other viruses (eg, influenza).6

    Limitations of this study include a potential sampling bias, as some participants may have presented to Mount Sinai Health System because of health concerns. Future studies should investigate long-term post–COVID-19 cognitive trajectories and the association with neuroimaging findings to assess potential mechanisms.

    Conclusions

    The association of COVID-19 with executive functioning raises key questions regarding patients’ long-term treatment. Future studies are needed to identify the risk factors and mechanisms underlying cognitive dysfunction as well as options for rehabilitation.

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    Article Information

    Accepted for Publication: August 17, 2021.

    Published: October 22, 2021. doi:10.1001/jamanetworkopen.2021.30645

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Becker JH et al. JAMA Network Open.

    Corresponding Author: Jacqueline H. Becker, PhD, Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 (jacqueline.becker@mountsinai.org).

    Author Contributions: Drs Becker and Wisnivesky had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Becker, Lin, Wisnivesky.

    Acquisition, analysis, or interpretation of data: Becker, Doernberg, Stone, Navis, Festa, Wisnivesky.

    Drafting of the manuscript: Becker, Stone, Wisnivesky.

    Critical revision of the manuscript for important intellectual content: Becker, Lin, Doernberg, Navis, Festa, Wisnivesky.

    Statistical analysis: Becker, Stone, Wisnivesky.

    Obtained funding: Wisnivesky.

    Administrative, technical, or material support: Becker, Lin, Doernberg, Wisnivesky.

    Supervision: Becker, Lin, Doernberg, Navis, Wisnivesky.

    Conflict of Interest Disclosures: Dr Wisnivesky reported receiving personal fees from Sanofi, Atea Pharmaceuticals, and Banook Group and grants from Sanofi, Regeneron Pharmaceuticals, and Arnold Consulting outside the submitted work. No other disclosures were reported.

    References
    1.
    Alnefeesi  Y, Siegel  A, Lui  LMW,  et al.  Impact of SARS-CoV-2 infection on cognitive function: a systematic review.   Front Psychiatry. 2021;11:621773. doi:10.3389/fpsyt.2020.621773PubMedGoogle Scholar
    2.
    Weintraub  S, Besser  L, Dodge  HH,  et al.  Version 3 of the Alzheimer Disease Centers’ neuropsychological test battery in the Uniform Data Set (UDS).   Alzheimer Dis Assoc Disord. 2018;32(1):10-17. doi:10.1097/WAD.0000000000000223PubMedGoogle ScholarCrossref
    3.
    Benedict  RH, Schretlen  D, Groninger  L, Brandt  J.  Hopkins Verbal Learning Test–Revised: normative data and analysis of inter-form and test-retest reliability.   Clin Neuropsychol. 1998;12(1):43-55. doi:10.1076/clin.12.1.43.1726Google ScholarCrossref
    4.
    Helms  J, Kremer  S, Merdji  H,  et al.  Neurologic features in severe SARS-CoV-2 infection.   N Engl J Med. 2020;382(23):2268-2270. doi:10.1056/NEJMc2008597PubMedGoogle ScholarCrossref
    5.
    Pandharipande  PP, Girard  TD, Jackson  JC,  et al; BRAIN-ICU Study Investigators.  Long-term cognitive impairment after critical illness.   N Engl J Med. 2013;369(14):1306-1316. doi:10.1056/NEJMoa1301372PubMedGoogle ScholarCrossref
    6.
    Beraki  S, Aronsson  F, Karlsson  H, Ogren  SO, Kristensson  K.  Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice.   Mol Psychiatry. 2005;10(3):299-308. doi:10.1038/sj.mp.4001545PubMedGoogle ScholarCrossref
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