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

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.

References

  1. Soriano, J. B., Murthy, S., Marshall, J. C., Relan, P. & Diaz, J. V. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect. Dis. 22, e102–e107 (2022).

    Article  CAS  PubMed  Google Scholar 

  2. Espinar-Herranz, K. et al. Memory, emotion, and quality of life in patients with long COVID-19. Brain Sci. 13, 1670 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Nalbandian, A., Desai, A. D. & Wan, E. Y. Post-COVID-19 condition. Annu. Rev. Med. 74, 55–64 (2023).

    Article  CAS  PubMed  Google Scholar 

  4. Nouraeinejad, A. Memory loss in patients with long COVID can be due to reduced hippocampal neurogenesis. Eur Arch Psychiatry Clin Neurosci. 18, 1–2 (2023).

    Google Scholar 

  5. Mansell, V., Hall Dykgraaf, S., Kidd, M. & Goodyear-Smith, F. Long COVID and older people. Lancet Healthy Longev. 3, e849–e854 (2022).

    Article  PubMed  Google Scholar 

  6. Liu, Y.-H. et al. One-year trajectory of cognitive changes in older survivors of COVID-19 in Wuhan, China: a longitudinal cohort study. JAMA Neurol. 79, 509–517 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liu, Y.-H. et al. Post-infection cognitive impairments in a cohort of elderly patients with COVID-19. Mol. Neurodegener. 16, 48 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. China Internet Information Center. China Focus: China releases measures to optimize COVID-19 response (China.org.cn, 2022); http://www.china.org.cn/china/Off_the_Wire/2022-11/11/content_78514718.htm

  9. Guan, W. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382, 1708–1720 (2020).

    Article  CAS  PubMed  Google Scholar 

  10. Zhao, Y. et al. The phenotype and prediction of long-term physical, mental and cognitive COVID-19 sequelae 20 months after recovery, a community-based cohort study in China. Mol. Psychiatry 28, 1793–1801 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Harrison, P. J. & Taquet, M. Neuropsychiatric disorders following SARS-CoV-2 infection. Brain 146, 2241–2247 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Del Brutto, O. H., Rumbea, D. A., Recalde, B. Y. & Mera, R. M. Cognitive sequelae of long COVID may not be permanent: a prospective study. Eur. J. Neurol. 29, 1218–1221 (2022).

    Article  PubMed  Google Scholar 

  13. Gonçalves, N. G. et al. Dissipating the fog: cognitive trajectories and risk factors 1 year after COVID‐19 hospitalization. Alzheimer’s Dementia 19, 3771–3782 (2023).

    Article  PubMed  Google Scholar 

  14. Blazhenets, G. et al. Slow but evident recovery from neocortical dysfunction and cognitive impairment in a series of chronic COVID-19 patients. J. Nucl. Med. 62, 910–915 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ley, H., Skorniewska, Z., Harrison, P. J. & Taquet, M. Risks of neurological and psychiatric sequelae 2 years after hospitalisation or intensive care admission with COVID-19 compared to admissions for other causes. Brain Behav. Immun. 112, 85–95 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Martin, E. M. et al. Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months. J. Neurol. 271, 46–58 (2024).

    Article  PubMed  Google Scholar 

  17. Schou, T. M., Joca, S., Wegener, G. & Bay-Richter, C. Psychiatric and neuropsychiatric sequelae of COVID-19—a systematic review. Brain Behav. Immun. 97, 328–348 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Carey, A. & Fossati, S. Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer’s disease and dementia: new evidence, potential therapeutic strategies, and biomarkers. Alzheimer’s Dementia 19, 671–695 (2023).

    Article  CAS  PubMed  Google Scholar 

  19. Barbiellini Amidei, C. et al. Association between age at diabetes onset and subsequent risk of dementia. JAMA 325, 1640–1649 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Dove, A. et al. The impact of diabetes on cognitive impairment and its progression to dementia. Alzheimer’s Dementia 17, 1769–1778 (2021).

    Article  PubMed  Google Scholar 

  21. Samaras, K. et al. Metformin use is associated with slowed cognitive decline and reduced incident dementia in older adults with type 2 diabetes: The Sydney Memory and Ageing Study. Diabetes Care 43, 2691–2701 (2020).

    Article  CAS  PubMed  Google Scholar 

  22. Smith, J. R. et al. Dementia occurring over a 32‐year follow‐up attributable to hypertension observed at different ages: implications for dementia prevention. Alzheimer’s Dementia 19, 3435–3447 (2023).

    Article  PubMed  Google Scholar 

  23. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected (WHO, 2020); https://www.who.int/publications/i/item/10665-332299

  24. Fong, T. G. et al. Telephone Interview for Cognitive Status: creating a crosswalk with the Mini‐Mental State Examination. Alzheimer’s Dementia 5, 492–497 (2009).

    Article  PubMed  Google Scholar 

  25. Fuh, J. L. et al. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a screening tool for dementia for a predominantly illiterate Chinese population. Neurology 45, 92–96 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Diener, H.-C. et al. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study. Lancet Neurol. 7, 875–884 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gülhan, P. Y., Arbak, P. M., Annakkaya, A. N., Balbay, E. G. & Balbay, Ö. A. An assessment of post-COVID-19 infection pulmonary functions in healthcare professionals. Am. J. Infect. Control 50, 1125–1132 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yang, X. et al. Two-year health outcomes in hospitalized COVID-19 survivors in China. JAMA Netw. Open 5, e2231790 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Frontera, J. A. et al. Trajectories of neurologic recovery 12 months after hospitalization for COVID-19: a prospective longitudinal study. Neurology 99, e33–e45 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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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.

Author information

Authors and Affiliations

Authors

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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The authors declare no competing interests.

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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 (2024). https://doi.org/10.1038/s43587-024-00667-3

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