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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.

Abstract

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.

References
1.
World Health Organization. WHO Coronavirus (COVID-19) Dashboard. Accessed February 21, 2022. https://covid19.who.int/
2.
Augustin  M , Schommers  P , Stecher  M ,  et al.  Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study.   Lancet Reg Health Eur. 2021;6:100122. doi:10.1016/j.lanepe.2021.100122PubMedGoogle ScholarCrossref
3.
Akbarialiabad  H , Taghrir  MH , Abdollahi  A ,  et al.  Long COVID, a comprehensive systematic scoping review.   Infection. 2021;49(6):1163-1186. doi:10.1007/s15010-021-01666-xPubMedGoogle ScholarCrossref
4.
Taquet  M , Luciano  S , Geddes  JR , Harrison  PJ .  Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA.   Lancet Psychiatry. 2021;8(2):130-140. doi:10.1016/S2215-0366(20)30462-4PubMedGoogle ScholarCrossref
5.
Vindegaard  N , Benros  ME .  COVID-19 pandemic and mental health consequences: systematic review of the current evidence.   Brain Behav Immun. 2020;89:531-542. doi:10.1016/j.bbi.2020.05.048PubMedGoogle ScholarCrossref
6.
Mao  L , Jin  H , Wang  M ,  et al.  Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China.   JAMA Neurol. 2020;77(6):683-690. doi:10.1001/jamaneurol.2020.1127PubMedGoogle ScholarCrossref
7.
Hosp  JA , Dressing  A , Blazhenets  G ,  et al.  Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19.   Brain. 2021;144(4):1263-1276. doi:10.1093/brain/awab009PubMedGoogle ScholarCrossref
8.
Hampshire  A , Trender  W , Chamberlain  SR ,  et al.  Cognitive deficits in people who have recovered from COVID-19.   EClinicalMedicine. 2021;39:101044. doi:10.1016/j.eclinm.2021.101044PubMedGoogle ScholarCrossref
9.
Liu  YH , Wang  YR , Wang  QH ,  et al.  Post-infection cognitive impairments in a cohort of elderly patients with COVID-19.   Mol Neurodegener. 2021;16(1):48. doi:10.1186/s13024-021-00469-wPubMedGoogle ScholarCrossref
10.
World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance, 28 January 2020. Accessed February 1, 2020. https://apps.who.int/iris/handle/10665/330893
11.
Guan  WJ , Ni  ZY , Hu  Y ,  et al; China Medical Treatment Expert Group for Covid-19.  Clinical characteristics of coronavirus disease 2019 in China.   N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032PubMedGoogle ScholarCrossref
12.
James  PA , Oparil  S , Carter  BL ,  et al.  2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).   JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427PubMedGoogle ScholarCrossref
13.
American Diabetes Association.  Classification and diagnosis of diabetes.   Diabetes Care. 2016;39(suppl 1):S13-S22. doi:10.2337/dc16-S005PubMedGoogle ScholarCrossref
14.
Vogelmeier  CF , Criner  GJ , Martinez  FJ ,  et al.  Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 report. GOLD executive summary.   Am J Respir Crit Care Med. 2017;195(5):557-582. doi:10.1164/rccm.201701-0218PPPubMedGoogle ScholarCrossref
15.
Fong  TG , Fearing  MA , Jones  RN ,  et al.  Telephone interview for cognitive status: creating a crosswalk with the mini-mental state examination.   Alzheimers Dement. 2009;5(6):492-497. doi:10.1016/j.jalz.2009.02.007PubMedGoogle ScholarCrossref
16.
Fuh  JL , Teng  EL , Lin  KN ,  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. 1995;45(1):92-96. doi:10.1212/WNL.45.1.92PubMedGoogle ScholarCrossref
17.
Mok  VC , Wong  A , Lam  WW ,  et al.  Cognitive impairment and functional outcome after stroke associated with small vessel disease.   J Neurol Neurosurg Psychiatry. 2004;75(4):560-566. doi:10.1136/jnnp.2003.015107PubMedGoogle ScholarCrossref
18.
Anderson  C , Teo  K , Gao  P ,  et al; ONTARGET and TRANSCEND Investigators.  Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies.   Lancet Neurol. 2011;10(1):43-53. doi:10.1016/S1474-4422(10)70250-7PubMedGoogle ScholarCrossref
19.
Diener  HC , Sacco  RL , Yusuf  S ,  et al; Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) study group.  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. 2008;7(10):875-884. doi:10.1016/S1474-4422(08)70198-4PubMedGoogle ScholarCrossref
20.
Burton  L , Tyson  SF .  Screening for cognitive impairment after stroke: a systematic review of psychometric properties and clinical utility.   J Rehabil Med. 2015;47(3):193-203. doi:10.2340/16501977-1930PubMedGoogle ScholarCrossref
21.
Pratt  LA , Weeks  JD , Goulding  MR .  Measures of cognitive functioning in the 1994-2000 second longitudinal study of aging.   Natl Health Stat Report. 2008;(2):1-15.PubMedGoogle Scholar
22.
Rabinovitz  B , Jaywant  A , Fridman  CB .  Neuropsychological functioning in severe acute respiratory disorders caused by the coronavirus: implications for the current COVID-19 pandemic.   Clin Neuropsychol. 2020;34(7-8):1453-1479. doi:10.1080/13854046.2020.1803408PubMedGoogle ScholarCrossref
23.
Miskowiak  KW , Johnsen  S , Sattler  SM ,  et al.  Cognitive impairments four months after COVID-19 hospital discharge: pattern, severity and association with illness variables.   Eur Neuropsychopharmacol. 2021;46:39-48. doi:10.1016/j.euroneuro.2021.03.019PubMedGoogle ScholarCrossref
24.
Taquet  M , Geddes  JR , Husain  M , Luciano  S , Harrison  PJ .  6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.   Lancet Psychiatry. 2021;8(5):416-427. doi:10.1016/S2215-0366(21)00084-5PubMedGoogle ScholarCrossref
25.
Mattioli  F , Stampatori  C , Righetti  F , Sala  E , Tomasi  C , De Palma  G .  Neurological and cognitive sequelae of COVID-19: a four month follow-up.   J Neurol. 2021;268(12):4422-4428. doi:10.1007/s00415-021-10579-6PubMedGoogle ScholarCrossref
26.
Hugon  J , Msika  EF , Queneau  M , Farid  K , Paquet  C .  Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex.   J Neurol. 2022;269(1):44-46. doi:10.1007/s00415-021-10655-xPubMedGoogle ScholarCrossref
27.
Chang  YL , Fennema-Notestine  C , Holland  D ,  et al; Alzheimer’s Disease Neuroimaging Initiative.  APOE interacts with age to modify rate of decline in cognitive and brain changes in Alzheimer’s disease.   Alzheimers Dement. 2014;10(3):336-348. doi:10.1016/j.jalz.2013.05.1763PubMedGoogle ScholarCrossref
28.
Singh  B , Mielke  MM , Parsaik  AK ,  et al.  A prospective study of chronic obstructive pulmonary disease and the risk for mild cognitive impairment.   JAMA Neurol. 2014;71(5):581-588. doi:10.1001/jamaneurol.2014.94PubMedGoogle ScholarCrossref
29.
Zlokovic  BV , Gottesman  RF , Bernstein  KE ,  et al.  Vascular contributions to cognitive impairment and dementia (VCID): a report from the 2018 National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke Workshop.   Alzheimers Dement. 2020;16(12):1714-1733. doi:10.1002/alz.12157PubMedGoogle ScholarCrossref
30.
Qin  Y , Wu  J , Chen  T ,  et al.  Long-term microstructure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations.   J Clin Invest. 2021;131(8):147329. doi:10.1172/JCI147329PubMedGoogle ScholarCrossref
31.
Kas  A , Soret  M , Pyatigoskaya  N ,  et al; on the behalf of CoCo-Neurosciences study group and COVID SMIT PSL study group.  The cerebral network of COVID-19-related encephalopathy: a longitudinal voxel-based 18F-FDG-PET study.   Eur J Nucl Med Mol Imaging. 2021;48(8):2543-2557. doi:10.1007/s00259-020-05178-yPubMedGoogle ScholarCrossref
32.
Solomon  JJ , Heyman  B , Ko  JP , Condos  R , Lynch  DA .  CT of postacute lung complications of COVID-19.   Radiology. 2021;301(2):211396. doi:10.1148/radiol.2021211396Google ScholarCrossref
33.
Huang  L , Yao  Q , Gu  X ,  et al.  1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.   Lancet. 2021;398(10302):747-758. doi:10.1016/S0140-6736(21)01755-4PubMedGoogle ScholarCrossref
34.
Zhou  M , Yin  Z , Xu  J ,  et al.  Inflammatory profiles and clinical features of coronavirus 2019 survivors 3 months after discharge in Wuhan, China.   J Infect Dis. 2021;224(9):1473-1488. doi:10.1093/infdis/jiab181PubMedGoogle ScholarCrossref
35.
Merkler  AE , Parikh  NS , Mir  S ,  et al.  Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza.   JAMA Neurol. 2020;77(11):1-7. doi:10.1001/jamaneurol.2020.2730PubMedGoogle ScholarCrossref
36.
Prudencio  M , Erben  Y , Marquez  CP ,  et al.  Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19.   Sci Transl Med. 2021;13(602):eabi7643. doi:10.1126/scitranslmed.abi7643PubMedGoogle ScholarCrossref
37.
Virhammar  J , Nääs  A , Fällmar  D ,  et al.  Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity.   Eur J Neurol. 2021;28(10):3324-3331. doi:10.1111/ene.14703PubMedGoogle ScholarCrossref
38.
Yang  AC , Kern  F , Losada  PM ,  et al.  Dysregulation of brain and choroid plexus cell types in severe COVID-19.   Nature. 2021;595(7868):565-571. doi:10.1038/s41586-021-03710-0PubMedGoogle ScholarCrossref
39.
Keren-Shaul  H , Spinrad  A , Weiner  A ,  et al.  A unique microglia type associated with restricting development of Alzheimer’s disease.   Cell. 2017;169(7):1276-1290.e17. doi:10.1016/j.cell.2017.05.018PubMedGoogle ScholarCrossref
40.
Song  E , Zhang  C , Israelow  B ,  et al.  Neuroinvasion of SARS-CoV-2 in human and mouse brain.   J Exp Med. 2021;218(3):e20202135. doi:10.1084/jem.20202135PubMedGoogle ScholarCrossref
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