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. 2022;88(3):1061-1074.
doi: 10.3233/JAD-220361.

Risk of Alzheimer's Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

Avram S Bukhbinder  1 , Yaobin Ling  2 , Omar Hasan, Xiaoqian Jiang  2 , Yejin Kim  2 , Kamal N Phelps  1 , Rosemarie E Schmandt  1 , Albert Amran  1 , Ryan Coburn  1 , Srivathsan Ramesh  1 , Qian Xiao  3 , Paul E Schulz  1
Affiliations

Risk of Alzheimer's Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

Avram S Bukhbinder et al. J Alzheimers Dis. 2022.

Abstract

Background: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer's disease (AD) risk in a general cohort of older US adults has not been characterized.

Objective: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database.

Methods: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up.

Results: From the unmatched sample of eligible patients (n = 2,356,479), PSM produced a sample of 935,887 flu-vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29-48) months; 5.1% (n = 47,889) of the flu-vaccinated patients and 8.5% (n = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59-0.61) and ARR was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.

Conclusion: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older.

Keywords: Alzheimer’s disease; cohort studies; incidence; influenza vaccines; pharmacoepidemiology; retrospective studies; vaccination.

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Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/22-0361r1).

Figures

Fig. 1
Fig. 1
Flowchart of Sampling Methodology. AD, Alzheimer disease; CDM, Clinformatics Data Mart; ICD, International Classification of Diseases. aAD diagnoses included dementia due to AD, unspecified dementia, and “senile” dementia. bAD medications were donepezil, galantamine, rivastigmine, and memantine. cExclusionary diagnoses were mild cognitive impairment, encephalopathy, and dementia (of any cause).
Fig. 2
Fig. 2
Overview of Primary and Secondary Analysis Designs. AD, Alzheimer disease; ATT, average treatment effect in the treated; ICD, International Classification of Diseases; PSM, propensity score matching. aVaccinations were not considered if preceded by a diagnosis code or medication record for AD. bThe results of Step 6 are shown in Table 3.
Fig. 3
Fig. 3
Estimated CIF Curve of Incident AD by Number of Influenza Vaccinations. Quantitative results from the regression model are presented in Supplementary Table 3.
See this image and copyright information in PMC

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