Donepezil-associated survival benefits among Alzheimer's disease patients are retained but not enhanced during COVID-19 infections

Elizabeth A Edmiston; Taissa A Bej; Brigid Wilson; Robin L P Jump; Joy A Phillips

doi:10.1177/20499361231174289

Donepezil-associated survival benefits among Alzheimer's disease patients are retained but not enhanced during COVID-19 infections

Ther Adv Infect Dis. 2023 May 22:10:20499361231174289. doi: 10.1177/20499361231174289. eCollection 2023 Jan-Dec.

Authors

Elizabeth A Edmiston¹, Taissa A Bej², Brigid Wilson^{2

3}, Robin L P Jump^{4

5}, Joy A Phillips⁶

Affiliations

¹ Interprofessional Improvement Research, Education and Clinical Center, VA Northeast Ohio Healthcare System, Cleveland, OH, USA.
² Geriatric Research Education and Clinical Center (GRECC), VA Northeast Ohio Healthcare System, Cleveland, OH, USA.
³ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁴ Geriatric Research Education and Clinical Center (GRECC), VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
⁵ Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ The Donald P. Shiley BioScience Center, San Diego State University, 5500 Campanile Drive MC 4650, San Diego, CA 92182-4650, USA.

Abstract

Background and aim: Donepezil is a front-line treatment for Alzheimer's disease. Donepezil treatment is associated with decreased risk of all-cause mortality. Specific protection is observed in pneumonia and cardiovascular disease. We hypothesized that donepezil treatment would improve mortality among Alzheimer's patients following infection with COVID-19. The objective of this study is to assess the influence of ongoing donepezil treatment on survival in Alzheimer's disease patients after polymerase chain reaction (PCR)-confirmed COVID-19 infection.

Methods: This is a retrospective cohort study. We conducted a national survey of Veterans with Alzheimer's disease to assess the influence of ongoing donepezil treatment on survival in Alzheimer's disease patients after PCR-confirmed COVID-19 infection. We assessed all-cause 30-day mortality stratified by COVID-19 infection and donepezil use, estimating odds ratios using multivariate logistic regression.

Results: Among people with Alzheimer's disease and COVID-19, all-cause 30-day mortality was 29% (47/163) for people taking donepezil compared with 38% (159/419) for those who were not. Among people with Alzheimer's disease without COVID-19, all-cause 30-day mortality was 5% (189/4189) for people taking donepezil compared with 7% (712/10,241) for those who were not. Adjusting for covariates, the decrease in mortality associated with donepezil did not differ between people with and without COVID-19 (interaction p = 0.710).

Conclusion: The known survival benefits of donepezil were retained but not found to be specific to COVID-19 among people with Alzheimer's disease.

Keywords: Alzheimer’s disease; COVID-19; SARS-CoV-2; donepezil; drug repurposing; retrospective analysis; veterans.