Influenza vaccination is associated with a reduced incidence of Alzheimer’s disease

Abstract

Abstract Background AD is a devastating disease and its pathophysiology is still largely unknown. No treatment has been shown to be efficacious, so prevention remains a very valuable approach. The objective of this work is to statistically test the relationship between influenza vaccination and the incidence of AD to identify a candidate for AD prevention. Method We used the Cerner Health Fact EHR dataset and excluded patients less than 60 years of age and included patients with ICD9 code ‘331.0’, i.e. Alzheimer’s disease. From this population, we constructed a cohort (N=311,424) for statistical analysis. Then we did propensity score matching (PMS) on AD with regard to patients’ demographics and then did PMS on influenza vaccine with regard to the age of AD onset and potential confounds such as prescribed medications. We obtained a balanced data set with respect to vaccinated patients and unvaccinated patients with PMS (N=9,066). To analyze the effects of frequency of vaccination, we divided the number of vaccinations by the length of time from the first vaccination timestamp to AD onset or the end of the observation. We performed a survival analysis on the entire cohort where development of AD was the end outcome. Result We obtained our results using chi‐square test, uni‐variate analysis, and time‐to‐event analysis. Our main outcomes are three aspects: (1) influenza vaccine significantly decreases AD prevalence (odds ratio 0.8309 with a p ‐value < 0.0001). (2) the frequency of influenza vaccine has a significant impact to inhibit AD onset (odds ratio 0.8736 with a p ‐value of 0.0342). (3) time‐to‐event analysis shows taking influenza vaccine at an earlier age leads to smaller AD risk than having vaccine at an older age (when the first vaccination age increases by 1, the hazard rate increases by 1.0924, p ‐value < 0.0001). Conclusion Analysis of a large clinical database suggests that there is a strong inverse relationship between AD and influenza vaccination. This result provides evidence that influenza vaccination may be a confounding factor in epidemiological studies of risk factors of Alzheimer’s Disease. Future studies may shed light on biological mechanisms to more deeply understand a promising, readily available candidate for preventing AD.