Patients aged 65 years or more who received a high-dose influenza vaccine had a lower risk of incident Alzheimer dementia during the first 25 months following vaccination compared with those who received a standard-dose vaccine. The study provides Class II evidence and does not establish causality.
In a retrospective cohort study using the IQVIA PharMetrics Plus for Academics claims database from 2014 to 2019, researchers analyzed 185,183 high-dose and 53,918 standard-dose person-trials among patients without prior cognitive impairment. Patients were followed for up to 3 years following vaccination, with incident Alzheimer dementia defined by diagnostic codes or prescriptions for donepezil, galantamine, rivastigmine, or memantine.
Using a target trial emulation framework with inverse probability weighting to adjust for confounding, high-dose vaccination was associated with a lower cumulative risk of Alzheimer dementia from months 1 to 25 in the per-protocol analysis. The maximum absolute risk difference was approximately 0.5%, corresponding to a number needed to treat of 185 at month 25. Risk ratios over this period ranged from about 0.78 to 0.89, indicating a consistently lower risk with high-dose vaccination.
Sex-stratified analyses suggested a longer-lasting and more robust association among women. Among men, a statistically significant association was observed only in intention-to-treat analyses from months 17 to 24.
In secondary analyses, sustained seasonal vaccination with a high-dose influenza vaccine was also associated with lower Alzheimer dementia risk, with the strongest effect observed at month 27 and a number needed to treat of 294.
When incident Alzheimer dementia was defined using medication claims only, there was no statistically significant difference between groups.
In a lagged sensitivity analysis, no statistically significant differences were observed during the first 7 months of follow-up, with lower risk emerging from months 8 to 28, suggesting the early apparent benefit may partly reflect reverse causality or detection bias.
The researchers noted that the underlying mechanism remains unclear and may reflect protection against influenza infection or non–infection-related immune effects.
However, several limitations should be noted. Follow-up was limited to up to 3 years. Mortality data were not available, and the database did not include sociodemographic or lifestyle variables. Incident Alzheimer dementia was defined using diagnostic codes and medication claims, and the researchers noted potential misclassification in claims-based data. When unspecified and senile dementia codes were excluded, the number of cases decreased by approximately 80%, and there were no statistically significant differences between groups. In addition, analyses restricted to certain subgroups suggested that residual confounding, including healthy-vaccinee bias, may have influenced the findings.
“[T]he risk of incident AD was significantly lower after [high-dose inactivated influenza vaccine] compared with [standard-dose inactivated influenza vaccine] for the first 25 months postvaccination, with a minimum NNT of 185.2 at month 25,” wrote lead study author Avram Samuel Bukhbinder of the Department of Neurology at The McGovern Medical School at UTHealth in Texas, and colleagues.
The researchers reported no relevant disclosures.
Source: Neurology
