A recent letter published in the journal Nature Aging by medical staff who worked in hospitals in Wuhan during the COVID-19 pandemic assessed cognitive trajectories over 2.5 years in older coronavirus disease 2019 (COVID-19) survivors.

Over one-tenth of the world’s population has had COVID-19. As the number of COVID-19 survivors increases, disease surveillance is increasingly crucial to examine the risk of post-infection symptoms. Deficits in executive functioning, verbal fluency, attention, learning and working memory, and processing speed have been observed among COVID-19 survivors, including those with mild illness.

Cognitive impairment is particularly prevalent in older adults with COVID-19. Previously, the authors reported that cognitive decline was highly prevalent a year after COVID-19 among older adults. Individuals with severe illness had the highest cognitive decline during the first six months post-discharge, which was further exacerbated by 12 months.

Letter: Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection. Image Credit: Donkeyworx / Shutterstock

About the study

In the present study, researchers investigated the cognitive trajectories of older adults over 2.5 years following COVID-19. They recruited hospitalized COVID-19 patients discharged between February 10 and April 10, 2020, from three hospitals in Wuhan. Follow-up analyses were performed 6, 12, and 30 months after discharge. Non-infected spouses of patients served as controls.

Eligible participants were aged ≥ 60. Individuals with cognitive impairment, neurological disorders, tumors, renal, cardiac, or hepatic failure, or a family history of dementia were excluded. Severe COVID-19 was defined as SARS-CoV-2 positivity plus at least one of the following conditions: respiratory rate ≥ 30 breaths per minute, severe respiratory distress, or (SpO₂)

Medical records were accessed for information on demographic and clinical characteristics. Telephone interviews were conducted at specified follow-up time points. Telephone interview for cognitive status (TICS)-40 scores were used to evaluate the cross-sectional cognitive status, with scores ≤ 20 or ≤ 12 indicating suspected mild cognitive impairment (MCI) or dementia syndrome, respectively.

The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) examined longitudinal cognitive changes during the first six months. Mann-Whitney U, chi-squared, and Kruskal-Wallis tests were used to compare characteristics between groups, ensuring robust statistical analysis. Multinomial logistic regression models explored the factors associated with longitudinal cognitive decline, adjusted for age, education, sex, body mass index (BMI), cognitive impairment (at six months), and delirium at the hospital.

Findings

Overall, 1,245 COVID-19 survivors and 358 controls completed the entire follow-up period. All survivors had only one episode of COVID-19, and controls were consistently infection-naïve throughout the follow-up. There were no differences in age, BMI, sex, education, and comorbidities between controls and survivors.

However, subjects with severe illness were older and had more comorbidities, higher frequencies of mechanical ventilation, high-flow oxygen therapy, intensive care admission, longer length of stay, and delirium than those with non-severe disease. Further, severe illness was more frequent among those on anti-bacterial, glucocorticoid, or immunoglobulin treatment.

The incident cognitive impairment was estimated at 19.1% among COVID-19 survivors, with severe cases showing a prevalence of 39.9% compared to 14.95% in non-severe cases and 14.25% in controls. At 30 months, severe cases had lower TICS-40 scores than non-severe cases and controls, and non-severe cases had lower scores than controls. More specifically, individuals with severe cases had a higher proportion of suspected dementia and mild cognitive impairment (MCI) than individuals with non-severe cases (dementia: 12.5% versus 1.74%, P

Severe cases had a higher incidence of suspected MCI and dementia than non-severe cases and controls. During the first follow-up year, severe cases experienced steeper cognitive decline than controls or non-severe cases. However, they had a lower rate of cognitive decline between 12 and 30 months compared to controls and non-severe cases.

Between 12 and 30 months after hospital discharge, individuals with severe cases (30.29%), individuals with non-severe cases (36.93%), and controls (34.36%) had comparable proportions of individuals with cognitive decline. Notably, controls and non-severe cases had comparable rates of cognitive decline. There was a higher proportion of individuals with progressive cognitive decline and a lower proportion of those with stable cognition among severe cases compared to controls and non-severe cases. However, individuals with severe cases had a lower frequency of stable cognition as defined by no cognitive status transition than individuals with non-severe cases (72.12% versus 89.68%, P

More severe cases achieved improved cognition between 6 and 30 months, transitioning from suspected MCI or dementia to cognitively normal status at a rate higher than controls and non-severe cases. Conversely, more severe cases achieved improved cognition, i.e., the transition from suspected dementia or MCI to cognitively normal status, between 6 and 30 months than controls and non-severe cases. Cognitive impairment at six months, hypertension, and severe COVID-19 were associated with longitudinal cognitive decline.

Conclusions

Taken together, cognitive impairment was observed among 10.2%, 12.5%, and 19.1% of COVID-19 survivors at 6, 12, and 30 months following discharge, respectively. It was notably high (39.9%) among severe cases. Cognitive trajectories were heterogeneous based on COVID-19 severity. The study’s limitations include the non-generalizability of findings to the general population or other viral variants and the use of a subjective assessment tool, which did not capture all cognitive subdomains, among others.

“All of the authors of this study are medical staff who worked in designated hospitals in Wuhan during the COVID-19 pandemic. We are deeply concerned about the potential long-term health consequences of COVID-19.”https://t.co/mNMdb0zUXh https://t.co/sCDCTbQedG

— Eric Topol (@EricTopol) July 23, 2024