SARS-CoV-2 Infection, Vaccination Status, and Dementia Risk: A Nested Case–Control Study

Abstract

Objectives: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may affect cognition, but its association with incident dementia remains inconsistent. We explored the association of SARS-CoV-2 infection and its vaccination with dementia risk in a nationwide sample of middle-aged and older adults. Methods: This nested case–control study used electronic healthcare data from Israel's largest health provider. Participants were dementia-free individuals aged ≥ 50 years at baseline (March 2020), followed up until May 2022. Incident dementia cases were matched to dementia-free controls using density sampling by age, sex, and date of entry to the study, with a ratio of 1:10. SARS-CoV-2 was defined by positive polymerase chain reaction (PCR) or institutional antigen tests. Multivariable conditional logistic regression models evaluated the association of SARS-CoV-2, its severity and vaccination, and pneumonia as a comparator, with dementia risk. Results: Among the 1,145,322 eligible participants, 27,280 dementia cases were matched to 272,800 controls. SARS-CoV-2 infection was associated with increased dementia risk (OR = 1.18; 95% CI 1.12–1.24; p < 0.001). This association was confined to hospitalized individuals with mild (OR = 2.39; 95% CI 2.07–2.76) and moderate-to-severe disease (OR = 1.93; 95% CI 1.70–2.20), was comparable to pneumonia (OR = 1.89; 95% CI 1.80–1.99), and was no longer evident after 6 months (OR = 1.04; 95% CI 0.96–1.12). COVID-19 vaccination was associated with 7%, 15%, and 31% lower dementia risk after two, three, and four doses, respectively. Unvaccinated individuals with prior COVID-19 had the highest dementia risk. Conclusions: Dementia diagnoses are increased after COVID-19, especially in hospitalized patients. Risk is comparable to other respiratory infections.