Chronic Periodontal Infections by Porphyromonas gingivalis and Risk of Alzheimer's Disease: A Systematic Review

Introduction: Chronic periodontitis is a persistent inflammatory disease driven by dysbiotic oral microbiota, particularly Porphyromonas gingivalis. Growing evidence suggests that periodontal infections may contribute to neurodegenerative processes through systemic inflammation, immune dysregulation, and direct microbial or toxin translocation to the central nervous system. P. gingivalis has been proposed as a potential modifiable risk factor for Alzheimer’s disease (AD), yet the strength and consistency of this association in human studies remain under debate. This systematic review aimed to evaluate whether chronic periodontitis associated with P. gingivalis increases the risk of Alzheimer’s disease.

Methods: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and Web of Science were searched for human studies published in English or Spanish between 2010 and 2025. Eligible designs included cohort, case–control, cross-sectional studies, clinical trials, and systematic reviews or meta-analyses assessing periodontitis, P. gingivalis, and Alzheimer’s disease or cognitive decline. Data extraction focused on study design, population characteristics, exposure definition, cognitive outcomes, and effect estimates.

Results: A total of 34 studies met the inclusion criteria, comprising 22 original observational studies, 3 clinical or interventional studies, and 9 systematic reviews or meta-analyses. Most longitudinal studies demonstrated a significant association between chronic periodontitis and increased risk of Alzheimer’s disease or accelerated cognitive decline, with reported hazard ratios ranging from approximately 1.5 to 2.5. Several studies identified elevated serum antibodies against P. gingivalis and detected bacterial DNA or gingipain proteases in postmortem Alzheimer’s brain tissue, supporting biological plausibility. Meta-analyses confirmed a statistically significant association, particularly in individuals with moderate-to-severe periodontitis.

Conclusions: Current evidence indicates a significant association between chronic periodontitis, especially infection with Porphyromonas gingivalis, and increased risk of Alzheimer’s disease. Although causality cannot yet be definitively established, periodontal disease represents a potentially modifiable risk factor for neurodegeneration.