Periodontitis, a chronic inflammatory disease affecting the supporting tissues of the teeth, has been linked to the onset of neurological diseases, including Alzheimer’s disease (AD). A primary mechanism connecting these two issues is oxidative stress caused by an imbalance between antioxidant defenses and reactive oxygen species (ROS) synthesis. This review compiles results from both animal and human studies that explore how oxidative stress resulting from periodontitis leads to neuroinflammation, mitochondrial dysfunction, and cognitive decline in AD. Studies in animals indicate that periodontal infections worsen brain oxidative damage, as evidenced by elevated lipid peroxidation markers, such as malondialdehyde (MDA), and indicators of oxidative DNA damage, including 8-hydroxy-2′-deoxyguanosine (8-OHdG). Additionally, significant reductions in crucial antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase, along with neuroinflammation and cognitive deficits, are observed in mouse models of induced periodontitis. Supporting evidence from human studies reveals lower total antioxidant capacity (TAC) in individuals with both Alzheimer’s disease (AD) and periodontitis, as well as increased systemic oxidative stress markers, such as advanced oxidation protein products (AOPRs). These findings suggest a mechanistic relationship through oxidative stress pathways between periodontal inflammation and neurodegeneration. Given the extensive impact of periodontitis, enhancing periodontal health could be a viable strategy to reduce oxidative damage and lower the risk of cognitive decline. Further research is needed to clarify causality and to investigate antioxidant treatments aimed at preventing or slowing the progression of AD in patients with periodontal disease.
Papadakis et al. (2025) studied this question.