Influenza infections and risk of Alzheimer’s disease

Imfeld, Patrick; Toovey, Stephen; Jick, Susan S.; Meier, Christoph

doi:10.1016/j.bbi.2016.03.014

Cited by 18 publications

(6 citation statements)

References 25 publications

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“…An association between flu infection and AD risk is supported by mouse studies demonstrating that peripheral infection of wild-type mice with non-neurotropic influenza strains induces excessive microglial activation and subsequent alteration of neuronal morphology, particularly in the hippocampus, that persists after infection resolution [38,41]; in APP/PS1 transgenic mice, peripheral influenza infection also induces persistent elevations of amyloid-␤ (A␤) plaque burden [42]. However, in contrast to these mouse studies, a case-control study of 38,926 older adults found no association between the number or severity of past influenza infections and AD risk [43]. Another influenza-specific mechanism potentially underlying the effects of influenza vaccination on AD risk is epitopic similarity between an influenza protein(s) and AD pathology.…”

Section: Hypothesized Mechanism(s)mentioning

confidence: 97%

Risk of Alzheimer’s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

Bukhbinder

Ling

Hasan³

et al. 2022

JAD

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Background: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including Veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer’s disease (AD) risk in a general cohort of older US adults has not been characterized. Objective: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database. Methods: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up. Results: From the unmatched sample of eligible patients (n = 2,356,479), PSM produced a sample of 935,887 flu–vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29–48) months; 5.1% (n = 47,889) of the flu-vaccinated patients and 8.5% (n = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59–0.61) and ARR was 0.034 (95% CI, 0.033–0.035), corresponding to a number needed to treat of 29.4. Conclusion: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older.

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Section: Hypothesized Mechanism(s)mentioning

confidence: 97%

Risk of Alzheimer’s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

Bukhbinder

Ling

Hasan³

et al. 2022

JAD

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“…Patients enrolled in the CPRD are broadly representative of the UK population with regard to age, gender, and ethnicity [25]. CPRD data have been used in previous studies on dementia, AD, and VaD [26][27][28][29][30].…”

Section: Study Design and Data Sourcementioning

confidence: 99%

Proton Pump Inhibitor Use and Risk of Developing Alzheimer’s Disease or Vascular Dementia: A Case–Control Analysis

et al. 2018

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“…We found no robust association between acute viral infections and dementia, consistent with an earlier study that reported no association between influenza and dementia. 28…”

Section: Discussionmentioning

confidence: 99%

Hospital-treated infectious diseases and the risk of dementia: multicohort study with replication in the UK Biobank

Heikkilä

et al. 2020

Preprint

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Background: Infectious diseases have been hypothesised to increase the risk of dementia. However, the evidence is sparse, captures only a limited range of infectious diseases, and relies on short follow-up periods. We assessed a wide range of severe (hospital-treated) bacterial and viral infections and their subtypes as risk factors for dementia in three large cohorts followed up for almost two decades and replicated the main findings in the UK Biobank. Methods: For primary analysis, we pooled individual-level data from three prospective cohort studies with a median follow up of 19 years (from 1986-2005 to 2012-2016) and a total of 273 125 dementia-free community-dwelling participants. The replication analysis with the UK Biobank was based on 492 146 individuals (median follow-up 9.0 years from 2006-2010 to 2018). We ascertained exposure to infectious diseases and their subtypes before dementia onset using linked records from national hospital inpatient registers. Incident dementia was identified from linked hospital inpatient and outpatient records, medication reimbursement entitlements, and death certificates. Findings: In the primary analysis based on 5.3 million person-years at risk, 88 099 participants had a hospital-treated infection before dementia onset and 3064 developed dementia. Gram-negative bacterial infections (hazard ratio [HR] 1.64; 95% confidence interval [CI] 1.25-2.14) and herpesvirus infections (HR 1.96; 95% CI 1.31-2.93) were robustly associated with an increased risk of dementia. For these infections, the relative risk of dementia remained similar when reverse causation and ascertainment biases were minimised by assessing only new dementia cases that occurred more than 10 years after the infection, and when comorbidities and potential confounders were considered. The associations were replicated in the UK Biobank with stronger relations observed for vascular dementia than Alzheimer's disease. In contrast to gram-negative bacterial and herpesvirus infections, the hazard ratio for all bacterial infections combined attenuated from 1.60 (95% CI 1.48-1.72) to 1.27 (95% CI 1.14-1.41) when bias was minimised. For all viral infections, the corresponding attenuation was from HR 1.63 (95% CI 1.32-2.00) to 1.19 (95% CI 0.87-1.62). Interpretation: Gram-negative bacterial infections and herpesvirus infections were associated with a moderately increased risk of dementia both in the short- and long-term. Hospital-treated bacterial and viral infections in general had only modest long-term associations with incident dementia.

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Influenza infections and risk of Alzheimer’s disease

Cited by 18 publications

References 25 publications

Risk of Alzheimer’s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

Risk of Alzheimer’s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

Proton Pump Inhibitor Use and Risk of Developing Alzheimer’s Disease or Vascular Dementia: A Case–Control Analysis

Hospital-treated infectious diseases and the risk of dementia: multicohort study with replication in the UK Biobank

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