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. 2023;95(2):703-718.
doi: 10.3233/JAD-221231.

The Impact of Routine Vaccinations on Alzheimer's Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study using Propensity Score Matching

Kristofer Harris  1 , Yaobin Ling  2 , Avram S Bukhbinder  1   3 , Luyao Chen  2 , Kamal N Phelps  1 , Gabriela Cruz  1 , Jenna Thomas  1 , Yejin Kim  2 , Xiaoqian Jiang  2 , Paul E Schulz  1
Affiliations

The Impact of Routine Vaccinations on Alzheimer's Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study using Propensity Score Matching

Kristofer Harris et al. J Alzheimers Dis. 2023.

Abstract

Background: Accumulating evidence suggests that adult vaccinations can reduce the risk of developing Alzheimer's disease (AD) and Alzheimer's disease related dementias.

Objective: To compare the risk for developing AD between adults with and without prior vaccination against tetanus and diphtheria, with or without pertussis (Tdap/Td); herpes zoster (HZ); or pneumococcus.

Methods: A retrospective cohort study was performed using Optum's de-identified Clinformatics® Data Mart Database. Included patients were free of dementia during a 2-year look-back period and were≥65 years old by the start of the 8-year follow-up period. We compared two similar cohorts identified using propensity score matching (PSM), one vaccinated and another unvaccinated, with Tdap/Td, HZ, or pneumococcal vaccines. We calculated the relative risk (RR) and absolute risk reduction (ARR) for developing AD.

Results: For the Tdap/Td vaccine, 7.2% (n = 8,370) of vaccinated patients and 10.2% (n = 11,857) of unvaccinated patients developed AD during follow-up; the RR was 0.70 (95% CI, 0.68-0.72) and ARR was 0.03 (95% CI, 0.02-0.03). For the HZ vaccine, 8.1% (n = 16,106) of vaccinated patients and 10.7% (n = 21,417) of unvaccinated patients developed AD during follow-up; the RR was 0.75 (95% CI, 0.73-0.76) and ARR was 0.02 (95% CI, 0.02-0.02). For the pneumococcal vaccine, 7.92% (n = 20,583) of vaccinated patients and 10.9% (n = 28,558) of unvaccinated patients developed AD during follow-up; the RR was 0.73 (95% CI, 0.71-0.74) and ARR was 0.02 (95% CI, 0.02-0.03).

Conclusion: Several vaccinations, including Tdap/Td, HZ, and pneumococcal, are associated with a reduced risk for developing AD.

Keywords: Alzheimer’s disease; cohort; dementia; diphtheria; epidemiology; herpes zoster; pertussis; pneumococcus; tetanus; vaccine.

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Conflict of interest statement

Paul E. Schulz is funded by the McCord Family Professorship in Neurology, the Umphrey Family Professorship in Neurodegenerative Disorders, multiple NIH grants, several foundation grants, and contracts with multiple pharmaceutical companies related to the performance of clinical trials. He serves as a consultant and speaker for Eli Lilly, Biogen, and Acadia Pharmaceuticals. Xiaoqian Jiang is funded by Christopher Sarofim Family Professorship, the CPRIT RR180012 award, UT Stars award, and NIH grants R01GM114612 and U01TR002062. Avram S. Bukhbinder is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review. All other authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
Flowchart of Sampling Methodology. The three main analyses using Tdap/Td, HZ, and pneumococcal vaccinations are shown. AD, Alzheimer’s disease; CDM, Optum’s de-identified Clinformatics® Data Mart Database; HZ, Herpes zoster; ICD, International Classification of Diseases; Tdap/Td, Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis/Tetanus toxoid, and reduced diphtheria toxoid. Figure adapted from Bukhbinder et al. [38]. Reprinted from Journal of Alzheimer’s Disease, vol. 88, no. 3, Bukhbinder AS, Ling Y, Hasan O, Jiang X, Kim Y, Phelps KN, Schmandt RE, Amran A, Coburn R, Ramesh S, Xiao Q, Schulz PE, Risk of Alzheimer’s disease following influenza vaccination: a claims-based cohort study using propensity score matching, pp. 1061-1074, 2022, with permission from IOS Press. The publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-220361.
Fig. 2
Fig. 2
Overview of Cohort Selection and Propensity Score Matching. AD, Alzheimer’s disease; ICD, International Classification of Diseases. Figure adapted from Bukhbinder et al. [38]. Reprinted from Journal of Alzheimer’s Disease, vol. 88, no. 3, Bukhbinder AS, Ling Y, Hasan O, Jiang X, Kim Y, Phelps KN, Schmandt RE, Amran A, Coburn R, Ramesh S, Xiao Q, Schulz PE, Risk of Alzheimer’s disease following influenza vaccination: a claims-based cohort study using propensity score matching, pp. 1061-1074, 2022, with permission from IOS Press. The publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-220361.
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