Does SARS-CoV-2 infection lead to cognitive deficits?

Reports of cognitive symptoms following SARS-CoV-2 infection led to several studies investigating cognitive deficits following COVID-19 infection. 

As an attempt to have a more robust study design, the authored leveraged:

• A multi-racial sample from USA communities of late-life adults
• Longitudinal cognitive assessments including pre- and post-infection
• Comprehensive confounder measurements and
• Systematic SARS-CoV-2 ascertainment to examine associations between infection history and short-term cognitive change

The study hypothesis was to find accelerated cognitive change accounting for pre-pandemic cognitive status and factors that may have been linked with infection susceptibility, cognition and dementia risk. 

Method

15792 participants were originally enrolled for Atherosclerosis Risk in Communities (ARIC) study between 1987-1989. 

3525 of those, provided consent on 1, March 2020 were eligible for SARS-CoV-2 ascertainment by the collaborative cohort of cohorts for COVID-19 research (C4R) study.

COVID-19 infection was confirmed by lab tests, health professional`s diagnosis and/or hospitalization records showing COVID-19 infection. 

All 3525 participants provided 1 pre-pandemic cognitive assessment in person during their visit 6 or 7. Pandemic era, phone-based assessment was provided by 2802 participants during visit 8 or 9. 

Analysis and Results

Association between SARS-CoV-2 infection and cognitive score change was observed. 

• Annualized rate of decline in global cognitive function among infected participants was greater (-0.10) compared with uninfected participants (-0.09). 
• Like with global cognition, domain specific score changes were seen only with hospitalized infection. A decline of executive function and memory was observed.

Reasons and rationale 

This study has observed larger cognitive decline in hospitalized SARS-CoV-2 infections when compared with non-hospitalized infections or non-infected participants over time. 

The most impacted domains were memory and executive functions; language was not affected. Cognitive decline could be attributed to following reasons:

• Infection severity was associated with symptoms lasting for 12 weeks or more supported by another study done in the U.K. 
• Previous research has shown cognitive decline in patients hospitalized for a range of infectious or non-infectious conditions. 
• Hospitalization-related factors such as pharmacological treatments, dietary changes, bed rest, or social isolation may also have contribute to cognitive changes.
• Prolonged infection could have resulted in pathological β-amyloid accumulation resulting in decreased cognition.
• The authors also found higher association between hospitalized SARS-CoV-2 and cognitive decline in diabetics, lower educated, or Black participants from the Forsyth center.

Study limitations

• Serological testing may have missed disease detection either just before infection occurred or when antibody levels waned and became undetectable leading to misclassification. 
• The exact dates of infection for all participants were not known. Hence, modest relative reductions in cognitive scores following severe infection are transient or sustained were not known. 
• Longitudinal studies with longer follow up are advised to understand long-term cognitive changes following COVID-19.

Conclusion

Conclusions of this research are consistent with previous studies suggesting severe SARS-CoV-2 infection might impact short-term cognition. Individuals hospitalized for SARS-CoV-2 infection, but not nonhospitalized SARS-CoV-2 infection, experienced accelerated decreases in global cognitive function scores.

Published: June 30, 2025. 

Source: doi:10.1001/jamanetworkopen.2025.18648

Authors

1. Ryan T. Demmer, PhD, MPH, Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, College of Medicine and Science, 200 First St SW, Rochester, MN 55905
2. Elizabeth C. Oelsner, MD, DrPH, Division of General Medicine, Columbia University Irving Medical Center, 622 W 168th St, PH9-105, New York, NY, 10032