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Risk of Developing Alzheimer Disease in Relation to Common Infections
Alejandra Camacho-Soto1, Irene Faust2, Osvaldo J Laurido-Soto3
1Department of Physical Medicine and Rehabilitation, The University of Kansas Medical Center, Kansas City, Kansas, USA, acamacho-soto@kumc.edu.
Introduction:
Many studies demonstrate positive associations between infections and Alzheimer disease (AD), suggesting that brain and/or systemic inflammation may impact AD pathogenesis. However, studies of meningitis and AD risk have been limited to animal models or small human cohorts in the USA. The objective of this study was to examine the relationship between incident AD and three different types of infections (meningitis, pneumonia, and urinary tract infections [UTIs]) using a population-based sample of US Medicare beneficiaries.
Methods:
We created a case-control dataset by frequency matching 4:1 (control:case) by age group, sex, and month/year of the date of AD diagnosis or control selection date. We identified 52,628 newly diagnosed AD cases and 210,512 population-based controls ≥67 years of age using comprehensive Medicare claims data from 2016 to 2018. We classified infections using ICD-9-CM and ICD-10-CM diagnosis codes. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between AD and each infection separately. We lagged exposures up to 18 months and examined hospitalization or comorbid sepsis as a proxy for infection severity. Covariates included age, sex, race/ethnicity, and health care utilization.
Results:
AD was positively associated with meningitis in individuals hospitalized without superimposed sepsis with a 6-month lag (OR = 2.713, 95% CI: 1.277-5.764), and UTIs without superimposed sepsis with an 18-month lag (OR = 1.231, 95% CI: 1.101-1.376), and with superimposed sepsis with an 18-month lag (OR = 1.388, 95% CI: 1.050-1.835). There was no association between AD and pneumonia in individuals hospitalized with or without superimposed sepsis. When examining infections that occurred in the outpatient setting, the association between AD and UTI remained positive yet attenuated at all time points, however, the association became inverse between AD and pneumonia.
Conclusion:
More severe infections, particularly meningitis, may be associated with a higher risk of AD, due to either unmasking of prodromal AD or acceleration of AD pathogenesis in susceptible individuals.
Insights
Severe infections like meningitis and urinary tract infections (UTIs) may increase Alzheimer disease (AD) risk. Pneumonia showed no association with AD in this large US Medicare study.
Area of Science:
- Neuroscience
- Epidemiology
- Infectious Diseases
Background:
- Growing evidence links infections to Alzheimer disease (AD) pathogenesis, potentially via inflammation.
- Previous studies on meningitis and AD risk were limited in scope and population.
- This study investigates the association between AD and common infections in a large US population.
Purpose of the Study:
- To examine the relationship between incident Alzheimer disease (AD) and three infections: meningitis, pneumonia, and urinary tract infections (UTIs).
- To assess the impact of infection severity (hospitalization, sepsis) on the AD association.
- To utilize a population-based sample of US Medicare beneficiaries for robust analysis.
Main Methods:
- A case-control study design was employed, matching 52,628 AD cases with 210,512 controls from Medicare claims (2016-2018).
- Infections were identified using ICD diagnosis codes, with analyses considering lagged exposures up to 18 months.
- Logistic regression models calculated adjusted odds ratios (ORs) for associations, controlling for covariates and examining infection severity.
Main Results:
- Meningitis hospitalization without sepsis showed a significant positive association with AD (OR=2.713) with a 6-month lag.
- Urinary tract infections (UTIs) were positively associated with AD, both with (OR=1.388) and without sepsis (OR=1.231), with an 18-month lag.
- No association was found between pneumonia and AD; outpatient UTIs showed an attenuated positive association, while outpatient pneumonia showed an inverse association.
Conclusions:
- More severe infections, particularly meningitis, may be linked to an increased risk of Alzheimer disease (AD).
- These findings suggest infections could either unmask prodromal AD or accelerate disease progression in susceptible individuals.
- The study highlights the potential role of specific infections in AD etiology within a large, real-world healthcare dataset.
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