Klebsiella Pneumoniae Infection Increases Risk of Alzheimer's Disease in the UK Biobank Cohort

Background: Infections, including bacterial pathogens, have been implicated in Alzheimer's disease (AD) risk. Klebsiella pneumoniae (K. pneumoniae) is a common hospital-acquired pathogen associated with significant inflammation, which may contribute to neurodegeneration. This study investigates the relationship between K. pneumoniae infections and AD in the UK Biobank cohort.

Methods: Using UK Biobank data, we assessed AD diagnoses based on linked healthcare records and identified K. pneumoniae infections using International Classification of Disease 10 Edition codes B96.1 and J15.0. A cohort of 502 494 participants was analyzed for AD incidence in relation to demographic factors, educational years, apolipoprotein E (APOE) isoforms, and history of K. pneumoniae infection. Logistic regression was used to assess the association between K. pneumoniae infection and AD risk.

Results: AD incidence was significantly higher among participants with a history of K. pneumoniae infection (1.0%) compared to those without (0.2%; P < 0.001, Fisher's exact test two-tailed). Logistic regression analysis revealed that K. pneumoniae infection was associated with an increased risk of AD (odds ratio = 3.32, P < 0.001), independent of age, sex, education, and APOE isoform. Additionally, AD risk was higher among ε4ε4 carriers and increased with age but decreased with additional years of education.

Conclusion: Our findings suggest that K. pneumoniae infection may be an independent risk factor for AD. This association underscores the need for further research into infection control and its role in mitigating neurodegenerative disease risk, particularly in populations susceptible to healthcare-associated infections.