OBJECTIVE: Neurological symptoms are commonly reported among individuals with postacute sequelae of COVID-19 (PASC), with cognitive impairment being the most common feature, but cognitive trajectories in PASC have not been clearly defined. The authors determined long-term cognitive changes in a cohort of individuals hospitalized with COVID-19, characterized their distinct cognitive trajectories, and identified factors associated with each trajectory at 36 months posthospitalization.
METHODS: The sample comprised 630 patients who were hospitalized with severe COVID-19 symptoms; 214 patients returned for at least one follow-up assessment over a 36-month period. Cognitive function, including attention, cognitive flexibility, processing speed, and memory, was evaluated by using BrainCheck, a validated digital platform, at 3-6, 12, 24, and 36 months posthospitalization. Longitudinal changes in cognitive performance and their associations with demographic factors, medical history, and neuropsychiatric symptoms were analyzed with linear mixed-effects models.
RESULTS: Four distinct cognitive trajectories over 36 months were identified and characterized. Group 1 (N=103, 48%) exhibited consistent normal cognitive function, group 2 (N=14, 7%) transitioned from unimpaired to impaired, group 3 (N=29, 14%) changed from impaired to unimpaired, and group 4 (N=68, 32%) showed persistent impairment across all domains. Poorer cognitive outcomes were associated with Hispanic ethnicity, although effects varied across domains.
CONCLUSIONS: As with many viral encephalitides, some patients showed stable normal or abnormal cognition or improved cognition over time. Surprisingly, however, a fourth subset exhibited delayed cognitive decline. This observation suggests that PASC-associated mechanisms, perhaps including chronic cerebral inflammation, may cause progressive cognitive impairment well after the initial infection clears.