tetano
Editor, Senior Moderator
Neurology
. 2026 Apr 28;106(8):e214782.
doi: 10.1212/WNL.0000000000214782. Epub 2026 Apr 1.
Risk of Alzheimer Dementia After High-Dose vs Standard-Dose Influenza Vaccination
Avram Samuel Bukhbinder[SUP] 1 2 [/SUP], Yaobin Ling[SUP] 3 [/SUP], Lauren Jhin[SUP] 1 [/SUP], Elizabeth He[SUP] 1 [/SUP], Kristofer Harris[SUP] 1 [/SUP], Mya Rodriguez[SUP] 4 [/SUP], Jenna Thomas[SUP] 1 [/SUP], Gabriela Cruz[SUP] 1 [/SUP], Kamal Phelps[SUP] 1 [/SUP], Yejin Kim[SUP] 3 [/SUP], Luyao Chen[SUP] 3 [/SUP], Xiaoqian Jiang[SUP] 3 [/SUP], Paul E Schulz[SUP] 1 [/SUP]
Affiliations
Background and objectives: Previous studies, including large cohort analyses comparing vaccinated and unvaccinated adults, suggest that routine immunizations such as inactivated influenza vaccines (IIVs) may reduce Alzheimer dementia (AD) risk. Whether AD risk differs after high-dose IIV (H-IIV) vs standard-dose IIV (S-IIV) remains unexamined. We hypothesized that AD risk would be lower among adults ≥65 years after H-IIV compared with S-IIV.
Methods: This retrospective cohort study analyzed data spanning 2014-2019 from IQVIA PharMetrics Plus for Academics, a US health care claims database. Eligible participants were ≥65 years with ≥2 years of continuous medical and pharmaceutical coverage and no previous diagnostic or pharmacotherapeutic indicators of cognitive impairment. Vaccinations were identified by name and Current Procedural Terminology codes. Participants were followed for up to 3 years postvaccination. Incident AD was defined using International Classification of Diseases codes and AD medication dispenses (anticholinesterase inhibitors, memantine). We emulated a target trial using sequential nested trials to align eligibility, treatment assignment, and time-zero with vaccination dates, preventing immortal time bias. Inverse probability weighting adjusted for measured confounding, emulated randomization, and mitigated selection bias. Effects were estimated as risk difference, number needed to treat (NNT), risk ratio; 95% CIs were obtained via bootstrapping. Secondary analyses examined potential effect modifiers such as sex.
Results: The H-IIV group included 120,775 unique participants (185,183 person-trials; mean age 74.4 years, SD 5.5; 57.3% female), and the S-IIV group included 44,022 participants (53,918 person-trials; mean age 73.0, SD 6.1; 56.4% female). H-IIV was associated with significantly lower AD risk during months 1-25 postvaccination (minimum NNT = 185.2 at 25 months). After sex stratification, risk reduction persisted longer among women (months 1-13, minimum NNT = 416.7) than men (months 17-24, significant only in intention-to-treat analysis, minimum NNT = 232.6).
Discussion: High-dose influenza vaccination is associated with reduced AD risk compared with standard-dose vaccination in adults ≥65 years, with a stronger effect among women. Significant study limitations included duration of follow-up (≤3 years) and lack of sociodemographic, lifestyle, biomarker, and mortality data. Further research is needed to clarify whether the observed difference reflects protection against influenza infection or non-infection-related mechanisms.
Classification of evidence: This study provides Class II evidence that treatment with H-IIV vs S-IIV was associated with decreased incident dementia in individuals ≥65 years of age captured in this US health care claims database.
. 2026 Apr 28;106(8):e214782.
doi: 10.1212/WNL.0000000000214782. Epub 2026 Apr 1.
Risk of Alzheimer Dementia After High-Dose vs Standard-Dose Influenza Vaccination
Avram Samuel Bukhbinder[SUP] 1 2 [/SUP], Yaobin Ling[SUP] 3 [/SUP], Lauren Jhin[SUP] 1 [/SUP], Elizabeth He[SUP] 1 [/SUP], Kristofer Harris[SUP] 1 [/SUP], Mya Rodriguez[SUP] 4 [/SUP], Jenna Thomas[SUP] 1 [/SUP], Gabriela Cruz[SUP] 1 [/SUP], Kamal Phelps[SUP] 1 [/SUP], Yejin Kim[SUP] 3 [/SUP], Luyao Chen[SUP] 3 [/SUP], Xiaoqian Jiang[SUP] 3 [/SUP], Paul E Schulz[SUP] 1 [/SUP]
Affiliations
- PMID: 41921123
- DOI: 10.1212/WNL.0000000000214782
Background and objectives: Previous studies, including large cohort analyses comparing vaccinated and unvaccinated adults, suggest that routine immunizations such as inactivated influenza vaccines (IIVs) may reduce Alzheimer dementia (AD) risk. Whether AD risk differs after high-dose IIV (H-IIV) vs standard-dose IIV (S-IIV) remains unexamined. We hypothesized that AD risk would be lower among adults ≥65 years after H-IIV compared with S-IIV.
Methods: This retrospective cohort study analyzed data spanning 2014-2019 from IQVIA PharMetrics Plus for Academics, a US health care claims database. Eligible participants were ≥65 years with ≥2 years of continuous medical and pharmaceutical coverage and no previous diagnostic or pharmacotherapeutic indicators of cognitive impairment. Vaccinations were identified by name and Current Procedural Terminology codes. Participants were followed for up to 3 years postvaccination. Incident AD was defined using International Classification of Diseases codes and AD medication dispenses (anticholinesterase inhibitors, memantine). We emulated a target trial using sequential nested trials to align eligibility, treatment assignment, and time-zero with vaccination dates, preventing immortal time bias. Inverse probability weighting adjusted for measured confounding, emulated randomization, and mitigated selection bias. Effects were estimated as risk difference, number needed to treat (NNT), risk ratio; 95% CIs were obtained via bootstrapping. Secondary analyses examined potential effect modifiers such as sex.
Results: The H-IIV group included 120,775 unique participants (185,183 person-trials; mean age 74.4 years, SD 5.5; 57.3% female), and the S-IIV group included 44,022 participants (53,918 person-trials; mean age 73.0, SD 6.1; 56.4% female). H-IIV was associated with significantly lower AD risk during months 1-25 postvaccination (minimum NNT = 185.2 at 25 months). After sex stratification, risk reduction persisted longer among women (months 1-13, minimum NNT = 416.7) than men (months 17-24, significant only in intention-to-treat analysis, minimum NNT = 232.6).
Discussion: High-dose influenza vaccination is associated with reduced AD risk compared with standard-dose vaccination in adults ≥65 years, with a stronger effect among women. Significant study limitations included duration of follow-up (≤3 years) and lack of sociodemographic, lifestyle, biomarker, and mortality data. Further research is needed to clarify whether the observed difference reflects protection against influenza infection or non-infection-related mechanisms.
Classification of evidence: This study provides Class II evidence that treatment with H-IIV vs S-IIV was associated with decreased incident dementia in individuals ≥65 years of age captured in this US health care claims database.