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

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.

Figure 1.. Screening Flowchart

Longitudinal cognitive decline was assessed using the Chinese version of the short form of the Informant Questionnaire on Cognitive Decline in the Elderly, current cognitive impairment using the Informant Questionnaire on Cognitive Decline in the Elderly and the Telephone Interview of Cognitive Status-40.

Figure 2.. Cognitive Trajectory of Patients With Severe and Nonsevere COVID-19 and Control Individuals During 1-Year Follow-up

Comparison of Telephone Interview of Cognitive Status-40 (TICS-40) scores among severe COVID-19 survivors, nonsevere COVID-19 survivors, and uninfected control individuals at 6 and 12 months was calculated using Wilcoxon (Mann-Whitney U) test. Proportions of participants with different cognitive statuses at 6 and 12 months were calculated using χ² test. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) scores ≥3.5 were considered indicative of cognitive decline. A decrease of ≥3 points on the TICS-40 from baseline during follow-up was considered indicative of clinically meaningful cognitive decline. H, Values adjusted for age, sex, education level, body mass index, and each comorbidity (Table 1) using linear mixed-effects models. Normalization of data was performed using minimum-maximum normalization. ^aDifference in mild cognitive impairment. ^bDifference in dementia.

Figure 3.. Factors Associated With Risk of Longitudinal Cognitive Decline in the Total Cohort

A, Cognitive impairment was defined by a Telephone Interview of Cognitive Status-40 score ≤20. In the investigation of risk factors for cognitive impairment at 12 months after patient discharge, ordinary logistic regression models were used. In the investigation of risk factors for longitudinal cognitive decline, multinomial regression models were used. All factors (including age, sex, education level, body mass index [BMI], and each comorbidity) different from the one examined were adjusted in the regression models. Each comorbidity was adjusted as an independent variable without accumulation. COPD indicates chronic obstructive pulmonary disease.