Influenza vaccination may have a protective effect against Alzheimer’s disease

In a recent study published in Alzheimer’s Disease JournalResearchers evaluated the risk of developing Alzheimer’s disease (AD) in individuals vaccinated against influenza in the United States (US).

Previous studies have reported a low risk of developing dementia after vaccination against influenza among veterans and certain individuals with severe and chronic medical disabilities. However, the effects of influenza vaccination on the accidental risk of AD in the elderly in the United States are not well characterized.

About research

In a current national retrospective cohort study, researchers compared the risk of developing AD between intramuscularly administered influenza vaccine recipients and non-recipients.

The analysis used a large US claims database from the Optum Clinformatics® Data Mart (CDM). The study participants were over 65 years old and did not have dementia. A cohort of influenza vaccine recipients and non-recipients was created using propensity score matching (PSM). The survey review and follow-up period was from September 1, 2009 to August 31, 2015, and from September 1, 2015 to August 31, 2019, respectively.

Individuals included in the study had one or more and two or more influenza vaccination records containing the International Classification of Diseases (ICD) code during the lookback and follow-up periods, respectively. The two cohorts were collated for demographic parameters, drug use, and the presence of comorbidity. If you were under 65 years of age at the beginning of the follow-up period, if you were diagnosed with mild cognitive impairment (MCI), dementia, or encephalopathy, and AD drugs (galantamine, donepezil, memantine, or rivastigmine).

Intranasal vaccines were recommended for individuals under the age of 50, and because the mechanism of action is significantly different from intramuscular formulations, individuals who received intranasal influenza vaccination were also excluded. Incident AD was considered when there were more than two AD-related records (such as the ICD code for diagnosing AD or the pharmacy claims for the four AD drugs listed above). Absolute risk reduction (ARR) and relative risk (RR) were determined to assess the impact of the influenza vaccine on AD risk during the follow-up period.

In the primary analysis, influenza vaccination during the follow-up period was evaluated as zero vaccination and two doses of one or more influenza vaccinations. The secondary analysis considered the total number of influenza vaccinations during the retrospective study period. Primary analysis data was analyzed based on the average therapeutic effect of influenza vaccination treatment (ATT) values ​​for AD risk, and secondary analysis data was analyzed by time-to-event analysis.

In addition, sensitivity analysis was performed by removing the ICD code for senile and non-specific dementia and expanding the study results from incident AD to ADRD (AD and related dementia). In addition, the lookback period and follow-up period were changed to 2 and 8 years, respectively, and the effect on the ATT value was evaluated considering individuals aged 75 and over (at the start of follow-up). In addition, Cox-type competitive risk regression modeling was used to calculate the subdistribution hazard ratio (sHR) to estimate the effect of influenza vaccination on the cumulative developmental function (CIF) of AD during the follow-up period. I did.

result

A total of 1,185,611 influenza vaccinated and 1,170,868 unvaccinated were identified and classified by PSM into 935,887 influenza vaccine recipient and non-recipient pairs. The average age of individuals was 73.7 years, most of whom (56.9%) were female and were followed for a median of 46 months. Of the matched individuals, 47,889 (5.1%) influenza vaccine recipients and 79,630 (8.5%) non-recipients developed incident AD during the follow-up period.

The values ​​for RR, ARR, and the number required for treatment (NNT) were 0.6, 0.034, and 29.4, respectively. In the sensitivity analysis, excluding the ICD codes for senile dementia and non-specific dementia, the ARR and RR values ​​were 0.02 and 0.65, respectively. The corresponding values ​​obtained, including all ADRD codes, were 0.033 and 0.60, respectively.

The sHR values ​​for the intramuscular influenza vaccination frequency and duration-influenza-vaccination interaction were 0.8 and 1.006, respectively. Similar to the primary ATT analysis with matched sample data, the time analysis to secondary events with mismatched sample data showed a negative correlation between influenza vaccination and AD risk.

Overall, the findings showed that influenza vaccination was associated with a 40% lower risk of developing AD in Americans over the age of 65. However, the underlying mechanism of this apparent immune protection needs further study. An association between influenza vaccination and symptom progression in patients with existing Alzheimer’s disease should also be evaluated.

The lead author of the study, Aviram S. Bukhbinder, said:

Influenza vaccination of the elderly has been found to reduce the risk of developing Alzheimer’s disease for several years. The strength of this preventive effect increased with the number of years a person was vaccinated with the flu vaccine each year. In other words, the incidence of Alzheimer’s disease was the lowest among those who consistently received the influenza vaccine each year.Future studies need to assess whether influenza vaccination is already associated with symptom progression in patients with Alzheimer’s disease... “

Also Paul. The lead author of the study, E. Schulz, MD concluded that:

We do not believe that the flu vaccine has a particular effect, as there is evidence that some vaccines may prevent Alzheimer’s disease. Instead, the immune system is complex, and we believe that some changes, such as pneumonia, may activate the immune system in ways that exacerbate Alzheimer’s disease. But other things that activate the immune system may do it in other ways-protecting against Alzheimer’s disease.Obviously, we have more to learn
How the immune system worsens or improves the consequences of this disease.. “