SARS‐CoV‐2 Infection, Vaccination Status, and Dementia Risk: A Nested Case–Control Study
Nika Zur, Nili Stein, Walid Saliba, Galit WeinsteinABSTRACT
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.