Clinically apparent Helicobacter pylori infection and the risk of incident Alzheimer's disease: A population‐based nested case‐control study

Antonios Douros, Zharmaine Ante, Carlo A. Fallone, Laurent Azoulay, Christel Renoux, Samy Suissa, Paul Brassard

Our population-based study assessed whether clinically apparent Helicobacter pylori infection (CAHPI) is associated with the risk of Alzheimer's disease (AD). We assembled a population-based cohort of all dementia-free subjects in the United Kingdom's Clinical Practice Research Datalink (UK CPRD), aged ≥50 years (1988-2017). Using a nested case-control approach, we matched each newly developed case of AD with 40 controls. Conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with CAHPI compared with no CAHPI during ≥2 years before the index date. We also used salmonellosis as a negative control exposure. Among 4,262,092 dementia-free subjects, 40,455 developed AD after a mean 11 years of follow-up. CAHPI was associated with an increased risk of AD (OR, 1.11; 95% CI, 1.01-1.21) compared with no CAHPI. Salmonellosis was not associated with the risk of AD (OR, 1.03; 95% CI, 0.82-1.29). CAHPI was associated with a moderately increased risk of AD. CAHPI was associated with an 11% increased risk of AD in subjects aged ≥50 years. The increase in the risk of AD reached a peak of 24% a decade after CAHPI onset. There was no major effect modification by age or sex. Sensitivity analyses addressing several potential biases led to consistent results.