Unlocking the Protective Potential of Upper Respiratory Infection Treatment Histories against Alzheimer's Disease: A Korean Adult Population Study

Abstract

With increasing interest in the inflammation-pathogen infection hypothesis and its potential links to Alzheimer's disease (AD) development, there is growing consideration of using upper respiratory infection (URI) treatments as interventions for AD. This nested case-control study explored the potential association between prior URI histories and AD development in a Korean adult population using the national health screening cohort data (2002-2019). The study included 26,920 AD patients and 107,680 matched control individuals, focusing on those seeking respiratory treatment. Logistic regression analyses assessed the impact of URI histories and treatment on AD risk while adjusting for covariates. Our results revealed that over a 1-year period, individuals with URI histories (≥1, ≥2, or ≥3 instances) exhibited decreasing probabilities of developing AD, with risk reductions of 19%, 15%, and 12%, respectively. Expanding our investigation to a 2-year period consistently showed a 17% reduction in AD risk. This effect remained robust across diverse demographic groups and after adjusting for covariates, encompassing comorbidities, hypertension, hyperlipidemia, blood glucose levels, and lifestyle factors. Subgroup analyses further substantiated this association. In conclusion, our findings cautiously suggest a potential protective role of prior URI treatment histories in mitigating the risk of AD development.

Keywords: Alzheimer’s disease; national health screening cohort; nested case–control study; upper respiratory infection.

Figure 1

A diagram illustrating the step-by-step process used to select participants for the study. Starting with the initial pool of 514,866 individuals in the Korean National Health Insurance Service—Health Screening Cohort (KNHIS-HSC) database, a meticulous selection process resulted in 26,920 patients diagnosed with Alzheimer’s disease (AD) being matched with 107,680 control participants. Matching was based on age, sex, income, and region of residence.

Figure 2

Forest plots illustrating the adjusted odds ratio and corresponding 95% confidence intervals (CIs) for demographic, lifestyle, and comorbid factors in relation to upper respiratory infections (URIs) for incident Alzheimer’s disease (AD) when participants had been diagnosed with URI ≥ 1 within 1 year before the index date.

Figure 3

Forest plots illustrating the adjusted odds ratio and corresponding 95% confidence intervals (CIs) for demographic, lifestyle, and comorbid factors in relation to upper respiratory infections (URIs) for incident Alzheimer’s disease (AD) when participants had been diagnosed with URI ≥ 1 within 2 years before the index date.