Risk of Developing Alzheimer Disease in Relation to Common Infections

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.