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Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection

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Abstract

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

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Fig. 1: Cognitive trajectories of COVID-19 patients and controls during the 30-month follow-up.
Fig. 2: Factors associated with longitudinal cognitive outcomes in COVID-19 survivors.

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Data availability

The raw data that support the findings are not publicly available due to confidentiality reasons and institutional ethics committee regulations but can be made available upon reasonable scientific request to the corresponding authors, Y.-H.L. and Y.-J.W., with each request subject to ethical and legislative review from the Ethics Committee of Daping Hospital. After internal review and approval, deidentified data and documents will be shared under agreements. The study protocol and statistical analyses are described in Methods.

Code availability

The R code used in the analyses is available at GitHub (https://github.com/wqinghua0906/cognition-and-Covid-19), but this study did not generate new or customized codes or software.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (no. 92249305 to Y.-J.W.), the Natural Science Foundation of Chongqing (no. CSTB2022NSCQ-LZX0042 to Y.-H.L.), High-Level Talents Innovation Project of PLA-Youth Talents of Science and Technology to Y.-H.L. and Master training project of Third Military Medical University to Y.-H.L.

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Author notes

  1. These authors contributed equally: Yu-Hui Liu, Quan-Xin Wu, Qing-Hua Wang.

Authors and Affiliations

  1. Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China

    Yu-Hui Liu, Qing-Hua Wang, Qiao-Feng Zhang, Yi Tang, Di Liu, Jing-Juan Wang, Xiao-Yu Liu, Ling-Ru Wang, Jie Zhu & Yan-Jiang Wang

  2. Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China

    Yu-Hui Liu, Qing-Hua Wang, Qiao-Feng Zhang, Yi Tang, Di Liu, Jing-Juan Wang, Xiao-Yu Liu, Ling-Ru Wang, Jie Zhu & Yan-Jiang Wang

  3. State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China

    Yu-Hui Liu & Yan-Jiang Wang

  4. Cadre Ward Two, General Hospital of Central Theater Command of PLA, Wuhan, China

    Quan-Xin Wu

  5. Department of Respiratory Medicine, Daping Hospital, Third Military Medical University, Chongqing, China

    Li Li

  6. Department of Oncology, General Hospital of Central Theater Command of PLA, Wuhan, China

    Cheng Xu

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Contributions

Y.-J.W. and Y.-H.L. designed this study and drafted the paper. Q.-X.W. and C.X. collected the clinical information of subjects. Q.-F.Z., Y.T., D.L., J.-J.W., X.-Y.L. and L.-R.W. performed the cognitive tests. Q.-H.W. performed the statistical analysis. L.L. and J.Z. performed critical reading of the paper.

Corresponding authors

Correspondence to Yu-Hui Liu or Yan-Jiang Wang.

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Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Aging thanks Guillem Navarra Ventura, Kathrin Finke and Sara Weisenbach for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Participant screening flowchart.

A total of 1,245 COVID-19 survivors and 358 uninfected spouses completed the 30-month follow-up study. The reasons for exclusion are specified in the flowchart. Abbreviations: IQCODE: Informant Questionnaire on Cognitive Decline in the Elderly; TICS-40: Telephone Interview for Cognitive Status-40.

Extended Data Fig. 2 Factors associated with longitudinal cognitive outcomes in COVID-19 survivors with severe cases.

(a) Factors associated with cognitive decline as defined by cognitive category conversion (cognitive status change from CN to MCI or dementia or from MCI to dementia). (b) Factors associated with progressive cognitive decline, which was defined as an IQCODE score >= 3.5 and a decrease in TICS-40 scores of 3 points or more during follow-up. All factors (including age, sex, education level, BMI, CAT score, and each comorbidity) different from the one examined were adjusted for in the regression models. Each comorbidity was adjusted for as an independent variable without accumulation. Two-sided p values are applied. Abbreviations: BMI, Body mass index; TICS-40: Telephone Interview for Cognitive Status-40; COPD, Chronic obstructive pulmonary disease.

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Liu, YH., Wu, QX., Wang, QH. et al. Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection. Nat Aging 4, 1186–1193 (2024). https://doi.org/10.1038/s43587-024-00667-3

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