As far fetched that it may sound, there is growing evidence that flu vaccination is associated with lower risk of being diagnosed with Alzheimer’s Disease (AD).¹

The most compelling evidence to date comes from a 2022 retrospective, propensity-matched study involving a nationwide sample of over 2 million U.S. adults ≥ 65 years old.¹  This study found a 40% reduction in the risk of incident AD during the 4-year follow-up period when individuals receiving at least 1 dose of flu vaccine were compared to those who did not receive flu vaccination during the study period (number needed to treat-NTT 29.4). 

Despite its limitations, the results of the above study were concordant with those of several smaller studies that found an association between flu vaccination and lower risk of dementia of any cause.^1-3  A 2022 meta-analysis also concluded that flu vaccination was associated with significantly lower risk (33%) of dementia among older people. Interestingly, in a study involving veterans, receipt of ≥6 doses of flu vaccines (not fewer) was associated with lower risk of dementia.⁴

Several hypotheses have been posited to explain the potential beneficial impact of flu vaccination on the risk of dementia, including: 1. Influenza-specific mechanisms, such as mitigation of damage secondary to influenza infection and/or epitopic similarity between influenza proteins and AD pathology; 2. Non-influenza-specific training of the innate immune system; and 3. Non-influenza-specific changes in adaptive immunity via lymphocyte-mediated cross-reactivity.¹

So, in addition to its protective effect against severe influenza,⁵ and its association with lower risk of hospitalization for cardiac disease and stroke and reduction in death due to combined cardiovascular disease events (eg, heart attacks/strokes),  flu vaccination may be protective against AD! Who would have thought that a simple vaccine may have far reaching health benefits?

Bonus Pearl: Did you know that mice infected with non-neurotropic influenza strains have been found to have excessive microglial activation and subsequent alteration of neuronal morphology, particularly in the hippocampus, and that in APP/PS1 transgenic mice, peripheral influenza infection induces persistent elevations of amyloid- (A) plaque burden?¹  Intriguing indeed!!!

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References

1. Bukhbinder AS, Ling Y, Hasan O, et al. Risk of Alzheimer’s disease following influenza vaccination: A claims-based cohort study using propensity score matching. Journal of Alzheimer’s Disease 2022; 88:1061-1074. https://pubmed.ncbi.nlm.nih.gov/26945371/  
2. Liu JC, Hsu YP, Kao PF, et al. Influenza vaccination reduces dementia risk in chronic kidney disease patients: A population-based cohort study. Medicine (Baltimore) 2016 95 :32868. https://pubmed.ncbi.nlm.nih.gov/26945371/
3. Wiemken TL, Salas J, Hoft DF, et al. Dementia risk following influenza vaccination in a large veteran cohort. Vaccine 2021;39:5524-5531. https://pubmed.ncbi.nlm.nih.gov/34420785/
4. Veronese N, Demurtas J, Smith L, et al. Influenza vaccination reduces dementia risk: A systematic review and meta-analysis. Ageing Res Rev 2022;73:101534. https://pubmed.ncbi.nlm.nih.gov/34861456/
5. Godoy P, Romero A, Soldevila N, et al. Influenza vaccine effectiveness in reducing severe outcomes over six influenza seasons, a case-cae analysis, Spain, 2010/11 to 2015/16.  Euro Surveill 2018;23:1700732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208006/
6. Hosseini S, Michaelsen-Preusse K, Schughart K, et al. Long-term consequences of non-neurotropic H3N2 influenza A virus infection for the progression of Alzheimer’s Disease symptoms. Front. Cell. Neurosci 28 April 2021; https://doi.org/10.3389/fncel.2021.643650 https://www.frontiersin.org/articles/10.3389/fncel.2021.643650/full

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!