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One-Year Trajectory of Cognitive Changes in Older Survivors of COVID-19 in Wuhan, ChinaA Longitudinal Cohort Study

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Key Points

Question  What is the dynamic trajectory of cognitive changes in the elderly population surviving COVID-19?

Findings  In this cohort study of 1438 COVID-19 survivors 60 years and older who were discharged from COVID-19–designated hospitals in Wuhan, China, the incidence of cognitive impairment was higher in COVID-19 survivors, especially those with severe cases, compared with uninfected participants during a 1-year follow-up period.

Meaning  The findings suggest that long-term cognitive decline is common after SARS-CoV-2 infection, indicating the necessity of evaluating the impact of the COVID-19 pandemic on the future dementia burden worldwide.


Importance  Determining the long-term impact of COVID-19 on cognition is important to inform immediate steps in COVID-19 research and health policy.

Objective  To investigate the 1-year trajectory of cognitive changes in older COVID-19 survivors.

Design, Setting, and Participants  This cohort study recruited 3233 COVID-19 survivors 60 years and older who were discharged from 3 COVID-19–designated hospitals in Wuhan, China, from February 10 to April 10, 2020. Their uninfected spouses (N = 466) were recruited as a control population. Participants with preinfection cognitive impairment, a concomitant neurological disorder, or a family history of dementia were excluded, as well as those with severe cardiac, hepatic, or kidney disease or any kind of tumor. Follow-up monitoring cognitive functioning and decline took place at 6 and 12 months. A total of 1438 COVID-19 survivors and 438 control individuals were included in the final follow-up. COVID-19 was categorized as severe or nonsevere following the American Thoracic Society guidelines.

Main Outcomes and Measures  The main outcome was change in cognition 1 year after patient discharge. Cognitive changes during the first and second 6-month follow-up periods were assessed using the Informant Questionnaire on Cognitive Decline in the Elderly and the Telephone Interview of Cognitive Status-40, respectively. Based on the cognitive changes observed during the 2 periods, cognitive trajectories were classified into 4 categories: stable cognition, early-onset cognitive decline, late-onset cognitive decline, and progressive cognitive decline. Multinomial and conditional logistical regression models were used to identify factors associated with risk of cognitive decline.

Results  Among the 3233 COVID-19 survivors and 1317 uninfected spouses screened, 1438 participants who were treated for COVID-19 (691 male [48.05%] and 747 female [51.95%]; median [IQR] age, 69 [66-74] years) and 438 uninfected control individuals (222 male [50.68%] and 216 female [49.32%]; median [IQR] age, 67 [66-74] years) completed the 12-month follow-up. The incidence of cognitive impairment in survivors 12 months after discharge was 12.45%. Individuals with severe cases had lower Telephone Interview of Cognitive Status-40 scores than those with nonsevere cases and control individuals at 12 months (median [IQR]: severe, 22.50 [16.00-28.00]; nonsevere, 30.00 [26.00-33.00]; control, 31.00 [26.00-33.00]). Severe COVID-19 was associated with a higher risk of early-onset cognitive decline (odds ratio [OR], 4.87; 95% CI, 3.30-7.20), late-onset cognitive decline (OR, 7.58; 95% CI, 3.58-16.03), and progressive cognitive decline (OR, 19.00; 95% CI, 9.14-39.51), while nonsevere COVID-19 was associated with a higher risk of early-onset cognitive decline (OR, 1.71; 95% CI, 1.30-2.27) when adjusting for age, sex, education level, body mass index, and comorbidities.

Conclusions and Relevance  In this cohort study, COVID-19 survival was associated with an increase in risk of longitudinal cognitive decline, highlighting the importance of immediate measures to deal with this challenge.

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Article Information

Accepted for Publication: February 4, 2022.

Published Online: March 8, 2022. doi:10.1001/jamaneurol.2022.0461

Corresponding Author: Yan-Jiang Wang, MD, PhD, Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing 400042, China (yanjiang_wang@tmmu.edu.cn).

Author Contributions: Drs Liu and YJ Wang 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. Drs Liu, Chen, QH Wang, and YR Wang contributed equally to this work.

Concept and design: Y Liu, Y Chen, YJ Wang.

Acquisition, analysis, or interpretation of data: Y Liu, Y Chen, Q Wang, L Wang, Jiang, Yang, X Chen, Y Li, Cen, C Xu, Zhu, W Li, YR Wang, Zhang, J Liu, Z Xu.

Drafting of the manuscript: Y Liu, Y Chen, Cen, YJ Wang.

Critical revision of the manuscript for important intellectual content: Y Liu, Y Chen, Q Wang, L Wang, Jiang, Yang, X Chen, Y Li, C Xu, Zhu, W Li, Ye-Ran Wang, Zhang, J Liu, Z Xu, YJ Wang.

Statistical analysis: Y Liu, Y Chen, Q Wang, Zhang.

Obtained funding: Y Liu.

Administrative, technical, or material support: Yang, Cen, Zhu, Zhang, Z Xu.

Supervision: Y Chen, Zhang, YJ Wang.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study is supported by the National Natural Science Foundation of China (81930028 to Dr YJ Wang, 81971024 to Dr Liu).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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