Linking periodontitis and Alzheimer’s disease: systemic inflammation as a shared mechanism

Periodontitis is a multifactorial disease that leads to the progressive destruction of the tooth’s supporting apparatus in the presence of bacterial plaque, the primary etiological agent; as responsible for systemic inflammation, it can activate the host’s immune response. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder characterized by a progressive cognitive decline in which inflammation plays a significant pathogenic role. This narrative review examines the most recent scientific evidence on the already established association between periodontal disease and Alzheimer’s disease. Articles published between 1984 and June 2024 were selected through searches conducted in the PubMed and Google Scholar databases, using the keywords “Periodontitis and Alzheimer’s disease”, “Periodontitis”, and “Alzheimer’s disease”. No language restrictions were applied, and only full-text articles were considered. Eligible studies included those involving humans, animals, and in vitro models, as well as systematic reviews and meta-analyses. Duplicates and studies not directly relevant to the topic were excluded. After applying these initial criteria, 179 articles were identified. Following a more detailed assessment, 72 articles were selected for inclusion in this review. The excluded studies were omitted due to limited relevance, redundancy with more comprehensive or recent publications, methodological limitations, or insufficient data for meaningful analysis. The final 72 articles were evaluated based on their methodology, key findings, and clinical implications. Periodontitis and AD often coexist. Periodontal patients are more likely to suffer from AD. Bacterial colonization of the periodontium, responsible either for a chronic and acute local inflammatory process, can extend to the brain via the bloodstream or the trigeminal nerve, as showed by post-mortem studies. Etiopathogenesis of periodontitis and AD is different; however, these pathologies share common risk factors that can influence their development, severity, and progression. Among those mechanisms, the most relevant is systemic inflammation, and a connection between periodontitis and AD was found in most papers; however, longitudinal and large-scale studies are needed to fully understand the deep mechanisms of this relationship.