Analysis of Molecular Aspects of Periodontitis as a Risk Factor for Neurodegenerative Diseases: A Single-Center 10-Year Retrospective Cohort Study

Neurodegenerative diseases (NDDs) represent a considerable global health burden with no definitive treatments. Emerging evidence suggests that periodontitis may contribute to NDD through shared inflammatory, microbial, and genetic pathways. A retrospective cohort design was applied to analyze hospital records from 2012-2022 and to determine whether periodontitis independently increases NDD risk when accounting for major cardiovascular, cerebrovascular, metabolic, and inflammatory confounders. Likelihood ratio-based Cox regression tests and Weibull survival models were applied to assess the association between periodontitis and NDD risk. Model selection was guided by Akaike and Bayesian information criteria, while Harrell's C-index and receiver operating characteristic curves evaluated predictive performance. Periodontitis demonstrated an independent association with neurodegenerative disease risk (HR 1.43, 95% CI 1.02-1.99). Cerebral infarction conferred the highest hazard (HR 4.81, 95% CI 2.90-7.96), while pneumonia (HR 1.96, 95% CI 1.05-3.64) and gastroesophageal reflux disease (HR 2.82, 95% CI 1.77-4.51) also showed significant increases in risk. Older individuals with periodontitis are at heightened risk of neurodegenerative disease, an effect further intensified by cerebrovascular, cardiometabolic, and gastroesophageal conditions. Pneumonia also emerged as an independent pathophysiological factor that may accelerate disease onset or progression. Attention to oral and systemic factors through coordinated clinical management may mitigate the onset and severity of neurodegeneration.