Flu and pneumonia vaccinations may reduce Alzheimer's risk

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Flu and pneumonia vaccinations are associated with reduced risk of Alzheimer’s disease, according to research reported at the Alzheimer’s Association International Conference® (AAIC®) 2020.

The research studies reported at AAIC 2020 suggest:
At least one flu vaccination was associated with a 17% reduction in Alzheimer’s incidence. More frequent flu vaccination was associated with another 13% reduction in Alzheimer’s incidence and vaccination against pneumonia between ages 65 and 75 reduced Alzheimer’s risk by up to 40% depending on individual genes.

“With the COVID-19 pandemic, vaccines are at the forefront of public health discussions. It is important to explore their benefit in not only protecting against viral or bacterial infection but also improving long-term health outcomes,” said Dr Maria C Carrillo, Alzheimer’s Association chief science officer. “It may turn out to be as simple as if you’re taking care of your health in this way – getting vaccinated – you’re also taking care of yourself in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” Carrillo said. “This research, while early, calls for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age.”

Previous research has suggested vaccinations may have a protective factor against cognitive decline, but there have been no large, comprehensive studies focused on the influenza (flu) vaccine and Alzheimer’s disease risk, specifically. To address this gap, Albert Amran, a medical student at McGovern Medical School at The University of Texas Health Science Centre at Houston, and team, investigated a large American health record dataset (n=9,066).

Amran and team found having one flu vaccination was associated with a lower prevalence of Alzheimer’s (odds ratio 0.83, p<0.0001), and among vaccinated patients receiving the flu vaccine more frequently was associated with an even lower prevalence of Alzheimer’s (odds ratio 0.87, p=0.0342). Thus, people that consistently got their annual flu shot had a lower risk of Alzheimer’s. This translated to an almost 6% reduced risk of Alzheimer’s disease for patients between the ages of 75-84 for 16 years.

The researchers found the protective association between the flu vaccine and the risk of Alzheimer’s was strongest for those who received their first vaccine at a younger age – for example, the people who received their first documented flu shot at age 60 benefitted more than those who received their first flu shot at age 70.

“Our study suggests that regular use of a very accessible and relatively cheap intervention – the flu shot – may significantly reduce risk of Alzheimer’s dementia,” Amran said. “More research is needed to explore the biological mechanism for this effect – why and how it works in the body – which is important as we explore effective preventive therapies for Alzheimer’s.”

Repurposing of existing vaccines may be a promising approach to Alzheimer’s disease prevention and Dr Svetlana Ukraintseva, associate research professor in the Biodemography of Aging Research Unit (BARU) at Duke University Social Science Research Institute, and team, investigated associations between pneumococcal vaccination, with and without an accompanying seasonal flu shot, and the risk of Alzheimer’s disease among 5,146 participants age 65+ from the Cardiovascular Health Study. The team also took into account a known genetic risk factor for Alzheimer’s — the rs2075650 G allele in the TOMM40 gene.

The researchers found that pneumococcal vaccination between ages 65-75 reduced risk of developing Alzheimer’s by 25-30% after adjusting for sex, race, birth cohort, education, smoking, and number of G alleles. The largest reduction in the risk of Alzheimer’s (up to 40%) was observed among people vaccinated against pneumonia who were non-carriers of the risk gene. Total number of vaccinations against pneumonia and the flu between ages 65 and 75 was also associated with a lower risk of Alzheimer’s; however, the effect was not evident for the flu shot alone.

“Vaccinations against pneumonia before age 75 may reduce Alzheimer’s risk later in life, depending on individual genotype,” Ukraintseva said. “These data suggest that pneumococcal vaccine may be a promising candidate for personalised Alzheimer’s prevention, particularly in non-carriers of certain risk genes.”

Abstract 1
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.

Albert Amran

Abstract 2
Background: Repurposing of existing vaccines could be a promising approach to Alzheimer’s disease (AD) prevention, exploiting potential heterologous effects of such vaccines. Adult vaccinations against pneumonia and the flu showed beneficial off-target effects on mortality and morbidity in some studies, including on dementia-related outcomes, suggesting that respective vaccines may be evaluated as repurposing candidates for prevention of AD and/or other dementias.
Method: We investigated associations between pneumococcal vaccine, with and without an accompanying flu shot, and the risk of AD among 5,146 elderly participants (65+) of the Cardiovascular Health Study, using covariates including sex, race, birth cohort, education, smoking, and rs2075650, a known genetic risk factor for AD in TOMM40 gene that may also be involved in brain vulnerability to infection through its connection to NECTIN2 (Yashin et al. 2018).
Result: Being vaccinated against pneumonia between ages 65-75 was associated with a reduction in the risk of AD afterwards (OR=0.70; P< 0.04) in logistic model with all covariates. A largest reduction in the risk of AD (OR = 0.62; P< 0.04) was observed in the vaccinated against pneumonia non-carriers of rs2075650 G allele (risk factor for AD). Total count of vaccinations against pneumonia and the flu between ages 65 and 75 was also associated with a lower risk of AD occurrence later in life (OR = 0.88; P< 0.01); however, the effect was not seen for the flu alone.
Conclusion: Vaccination against pneumonia before the age 75 may reduce AD risk later in life, especially in people without genetic risk factor for AD (rs2075650, G allele). These results suggest that pneumococcal vaccine may be a promising candidate for repurposing for personalized AD prevention in carriers of particular genotypes. Validation of these effects in higher power datasets is warranted.

Svetlana Ukraintseva


People who got at least one flu shot had a 17% reduction in risk, Amran says. And people who got regular vaccinations saw their risk drop another 13%. "More vaccinations meant less Alzheimer's," Amran says in an NPR report. But he cautions that the amount of benefit from flu vaccination could be different in a different group of people. "There is a protective effect," he says. "How much is something that needs to be quantified with a more intensive study."

Scientists don't know why vaccinations might reduce the risk of Alzheimer's. But previous research has hinted at a connection. And there are several potential explanations. One is that vaccines for the flu and pneumonia may be protective because the two diseases they are designed to prevent are known to affect the brain.

"Every time you have one of these infections you may experience a challenge to your memory and thinking," Carrillo says. And studies suggest that those events can increase a person's risk of Alzheimer's.

Another possibility involves evidence linking Alzheimer's to a general weakening in the immune system and to changes that allow more bacteria and viruses into the brain.

"So if we have some general means of improving immunity, it might help reduce Alzheimer's disease," Ukraintseva says.


AAIC 2020 material


AAIC 2020 abstracts


Full NPR report

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