Helicobacter pylori seropositivity and its association with incident all-cause and Alzheimer's disease dementia in large national surveys

Abstract

Introduction: Infectious agents were recently implicated in Alzheimer's disease (AD) and etiology of other dementias, notably Helicobacter pylori.

Methods: We tested associations of H. pylori seropositivity with incident all-cause and AD dementia and with AD-related mortality among US adults in a retrospective cohort study. Data from the National Health and Nutrition Surveys III, phase 1 (1988-1991) and 1999-2000 linked with Medicare and National Death Index registries, were used (baseline age ≥45 y, follow-up to 2013, N_pooled = 5927).

Results: A positive association between H. pylori seropositivity and AD mortality was found in men (hazard ratio_{adj, pooled} = 4.33, 95% confidence interval: 1.51-12.41, P = .006), which was replicated for incident AD and all-cause dementia, with hazard ratio_{adj, pooled} = 1.45 (95% confidence interval: 1.03-2.04, P = .035) and hazard ratio_{adj, III} = 1.44 (95% confidence interval: 1.05-1.98, P = .022), respectively. These associations were also positive among higher socioeconomic status groups.

Discussion: In sum, H. pylori seropositivity's direct association with AD mortality, all-cause dementia, and AD dementia was restricted to men and to higher socioeconomic status groups.

Keywords: Aging; Alzheimer's disease; Dementia; Helicobacter pylori; Mortality.

Fig. 1.

Participant flowchart. Sample 4, mean ± SD of follow-up time (months): AD deaths: NHANES III, phase I: 174.0 ± 86.1 NHANES 1999–00: 120.0 ± 38.1. Incident AD: NHANES III, phase I: 170.3 ± 86.5 NHANES 1999–00: 117.4 ± 40.7. Incident all-cause dementia: NHANES III, phase I: 165.3 ± 87.6 NHANES 1999–00: 114.7 ± 43.6. Additional missing data (n = 41 observations for pooled analysis, n = 38 for NHANES III, phase I, and n = 3 for NHANES 1999–00) is found for each type of analysis, given that some sample weights were not valid and/or observations end before enter (i.e., prevalent cases of AD and all-cause dementia). Abbreviations: AD, Alzheimer’ disease; H. pylori, Helicobacter pylori; NHANES, National Health and Nutrition Examination Surveys; SD, standard deviation.

Fig. 2.

Hazard rate of Alzheimer’s disease mortality by H. pylori seropositivity status from fully adjusted Cox PH models among (A) Men, (B) Women: NHANES III, phase 1 and NHANES 1999–00 (pooled sample). Analysis time is expressed in months. Smoothed hazard functions are obtained from the fully adjusted model (model 3) among men and women. Abbreviations: H. pylori, Helicobacter pylori; Hp IgG^–, H. pylori negative; Hp IgG⁺, H. pylori positive; NHANES, National Health and Nutrition Examination Surveys; PH, proportional hazards; IgG, Immunoglobulin G.