Chronic periodontitis and systemic inflammation in the elderly: implications for neurodegeneration.

Chronic periodontitis is increasingly recognized as a potential upstream contributor to neurodegenerative processes through sustained systemic inflammation, microbial dysbiosis, and blood-brain barrier (BBB) alterations. This review synthesizes human and experimental evidence linking periodontal pathogens-including but not limited to Porphyromonas gingivalis as well as broader dysbiotic consortia such as Tannerella forsythia, Treponema denticola, and other keystone oral taxa-to neuroinflammatory cascades associated with cognitive decline. Mechanistic insights highlight the roles of glial activation, proinflammatory cytokines, and polymicrobial virulence-mediated neuronal stress in bridging oral and brain pathology, while age-related factors such as immunosenescence and microbiome imbalance amplify systemic vulnerability. Human biomarker and imaging studies support an association between chronic periodontal inflammation and neurovascular dysfunction, suggesting that oral disease may act as a persistent peripheral amplifier of central immune activation. Recent research has expanded into biomarker discovery and translational implementation, yet progress remains limited by population heterogeneity, methodological variability, and regulatory complexity. Promising interventions-including anti-inflammatory therapies, oral hygiene optimization, probiotic or dietary modulation, and molecular strategies such as polymicrobial-targeted approaches, gingipain inhibition, and microRNA-based modulation-are discussed within emerging multi-omics and precision-medicine frameworks. Although standardization and longitudinal validation are still required, integrative approaches combining inflammatory, microbial, and genetic profiling may enable individualized risk assessment and targeted prevention. As global populations age, addressing the oral-brain axis offers a practical and modifiable pathway to lessen the burden of neurodegenerative diseases and support healthier cognitive aging.