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In Frontiers in medicine

Background : COVID-19 has been associated with an increased risk of incident dementia (post-COVID dementia). Establishing additional risk markers may help identify at-risk individuals and guide clinical decision-making.

Methods : We investigated pre-COVID psychotropic medication use (exposure) and 1-year incidence of dementia (outcome) in 1,755 patients (≥65 years) hospitalized with COVID-19. Logistic regression models were used to examine the association, adjusting for demographic and clinical variables. For further confirmation, we applied the Least Absolute Shrinkage and Selection Operator (LASSO) regression and a machine learning (Random Forest) algorithm.

Results : One-year incidence rate of post-COVID dementia was 12.7% (N = 223). Pre-COVID psychotropic medications (OR = 2.7, 95% CI: 1.8-4.0, P < 0.001) and delirium (OR = 3.0, 95% CI: 1.9-4.6, P < 0.001) were significantly associated with greater 1-year incidence of post-COVID dementia. The association between psychotropic medications and incident dementia remained robust when the analysis was restricted to the 423 patients with at least one documented neurological or psychiatric diagnosis at the time of COVID-19 admission (OR = 3.09, 95% CI: 1.5-6.6, P = 0.002). Across different drug classes, antipsychotics (OR = 2.8, 95% CI: 1.7-4.4, P < 0.001) and mood stabilizers/anticonvulsants (OR = 2.4, 95% CI: 1.39-4.02, P = 0.001) displayed the greatest association with post-COVID dementia. The association of psychotropic medication with dementia was further confirmed with Random Forest and LASSO analysis.

Conclusion : Confirming prior studies we observed a high dementia incidence in older patients after COVID-19 hospitalization. Pre-COVID psychotropic medications were associated with higher risk of incident dementia. Psychotropic medications may be risk markers that signify neuropsychiatric symptoms during prodromal dementia, and not mutually exclusive, contribute to post-COVID dementia.

Freudenberg-Hua Yun, Makhnevich Alexander, Li Wentian, Liu Yan, Qiu Michael, Marziliano Allison, Carney Maria, Greenwald Blaine, Kane John M, Diefenbach Michael, Burns Edith, Koppel Jeremy, Sinvani Liron


COVID-19, cognitive impairment, dementia, geriatric, post-COVID, psychotropic medication