People who have survived COVID-19 frequently complain of cognitive dysfunction, which has been described as brain fog. The prevalence of cognitive impairment post-COVID-19 and the association with disease severity are not well characterized. Previous studies on the topic have been limited by small sample sizes and suboptimal measurement of cognitive functioning.
We investigated rates of cognitive decline in COVID-19 survivors who were treated in outpatient settings, the emergency department (ED), or inpatient hospitals.
Methods
We analyzed data in this cross-sectional study from April 2020 to May 2021 from a cohort of COVID-19 patients followed through a Mount Sinai Health System registry. Study participants were 18 years or older, spoke English or Spanish, tested positive for SARS-CoV-2 or had positive serum antibodies, and had no history of dementia. Participant demographic characteristics (e.g., age, race, and ethnicity) were collected via self-report.
Cognitive functioning was assessed using well-validated neuropsychological measures: Numerical Span Forward (Attention) and Backward (Working Memory), Clue Making Test Part A and Part B (Processing Speed and Executive Functioning, respectively), Phonemic Fluency and categories (language), and the Hopkins Verbal Learning Test – Revised (encoding, recall, and recognition memory).
The Mount Sinai Health System Institutional Review Board approved this study, and informed consent was obtained from study participants. The study followed the publication Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
We calculated the frequency of impairment on each measure, defined as a z score less than or equal to 1.5 SD below the measure-specific age, educational level, and sex-adjusted norms.
Logistic regression assessed the association between cognitive impairment and COVID-19 care setting (outpatient, urgent care, or hospital), adjusting for race and ethnicity, smoking, body mass index, comorbidities, and depression. The threshold for statistical significance was α = .05 and the tests were 2-tailed. Analyzes were performed using SAS, version 9.4 (SAS Institute).
Results
The median (IQR) age of 740 participants was 49 (38-59) years, 63% (n = 464) were women, and the median (SD) time since COVID-19 diagnosis was 7.6 (2 ,7 months.
Participants self-identified as Black (15%), Hispanic (20%), or White (54%) or selected multiracial or other races and ethnicities (11%; other races included Asians [4.5%, n = 33)] and those who selected "other" as race).
The most prominent deficits were processing speed (18%, n = 133), executive functioning (16%, n = 118), phonemic fluency (15%, n = 111), and category fluency (20%, n = 111). n = 148), memory encoding (24%, n = 178), and memory retrieval (23%, n = 170).
In adjusted analyses, hospitalized patients were more likely to have deficits in attention (odds ratio [OR]: 2.8; 95% CI: 1.3-5.9), executive functioning (OR: 1. 8, 95% CI: 1.0-3.4), category fluency (OR: 3.0, 95% CI: 1.7-5.2), memory encoding (OR: 2.3 ; 95% CI: 1.3-4.1) and memory recovery (OR: 2.2; 95% CI: 1.3-3.8) than those in the outpatient group.
Patients treated in the ED were more likely to have impairments in category fluency (OR: 1.8; 95% CI: 1.1-3.1) and memory encoding (OR: 1 .7, 95% CI: 1.0-3.0) than those treated in the outpatient setting.
No significant differences in impairments in other domains were observed between groups.
Discussion
In this study, we found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were prevalent among hospitalized patients.
The relative preservation of recognition memory in the context of impaired encoding and memory suggests an executive pattern. This pattern is consistent with early reports describing a dysexecutive syndrome following COVID-19 and has considerable implications for occupational, psychological, and functional outcomes.
It is well known that certain populations (eg, older adults) may be particularly susceptible to cognitive decline following critical illness; However, in the relatively young cohort of the present study, a substantial proportion showed cognitive dysfunction several months after recovering from COVID-19. The findings of this study are generally consistent with those of research on other viruses (e.g., influenza).
Limitations of this study include potential sampling bias, as some participants may have presented to the Mount Sinai Health System due to health concerns. Future studies should investigate long-term cognitive trajectories post-COVID-19 and the association with neuroimaging findings to evaluate potential mechanisms.
Conclusions The association of COVID-19 with executive functioning raises key questions about the long-term treatment of patients. Future studies are needed to identify risk factors and mechanisms underlying cognitive dysfunction, as well as rehabilitation options. |
