Lehrer Steven, Rheinstein Peter H
Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York.
Severn Health Solutions, Severna Park, Maryland.
medRxiv. 2024 Nov 22:2024.11.21.24317739. doi: 10.1101/2024.11.21.24317739.
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.
Using UK Biobank data, we assessed AD diagnoses based on linked healthcare records and identified K. pneumoniae infections using ICD-10 codes B96.1 and J15.0. A cohort of 502,494 participants was analyzed for AD incidence in relation to demographic factors, educational years, APOE isoforms, and history of K. pneumoniae infection. Logistic regression was used to assess the association between K. pneumoniae infection and AD risk.
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 (OR = 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.
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.
包括细菌病原体在内的感染与阿尔茨海默病(AD)风险有关。肺炎克雷伯菌是一种常见的医院获得性病原体,与显著的炎症相关,这可能导致神经退行性变。本研究在英国生物银行队列中调查肺炎克雷伯菌感染与AD之间的关系。
利用英国生物银行的数据,我们根据关联的医疗记录评估AD诊断,并使用国际疾病分类第十版(ICD - 10)编码B96.1和J15.0识别肺炎克雷伯菌感染。对502494名参与者的队列分析了与人口统计学因素、受教育年限、载脂蛋白E(APOE)亚型以及肺炎克雷伯菌感染史相关的AD发病率。采用逻辑回归评估肺炎克雷伯菌感染与AD风险之间的关联。
有肺炎克雷伯菌感染史的参与者中AD发病率(1.0%)显著高于无感染史的参与者(0.2%;p < 0.001,双侧Fisher精确检验)。逻辑回归分析显示,肺炎克雷伯菌感染与AD风险增加相关(比值比[OR] = 3.32,p < 0.001),独立于年龄、性别、教育程度和APOE亚型。此外,ε4ε4携带者的AD风险更高,且随年龄增加而增加,但随额外受教育年限增加而降低。
我们的研究结果表明,肺炎克雷伯菌感染可能是AD的一个独立危险因素。这种关联强调了进一步研究感染控制及其在降低神经退行性疾病风险中的作用的必要性,特别是在易发生医疗相关感染的人群中。