Periodontal Inflammation Accelerates Osa Related Cognitive Impairment

Obstructive sleep apnea (OSA) and chronic periodontitis are both recognized risk factors for cognitive dysfunction. This study aims to investigate whether chronic periodontitis contributes to and accelerates the onset and progression of OSA-induced cognitive dysfunction, as well as elucidates the underlying mechanisms. By constructing mouse models of OSA and chronic periodontitis and employing methodologies including whole-brain tissue clearing, functional magnetic resonance imaging (fMRI) of the mouse brain, behavioral, histochemical, and molecular biological techniques was used to clarify the role of chronic periodontitis in OSA-induced cognitive dysfunction and to explore the potential molecular mechanisms involved. In the animal models, chronic periodontitis was shown to accelerate the onset of cognitive dysfunction in OSA mice, characterized by increased serum levels of TNF-α, IL-1β, and IL-18, activation of microglia and astrocytes in the hippocampus, heightened oxidative stress, alterations in neuronal mitochondrial morphology and function, reduced neuronal count, and elevated expression of HIF-1α, HMGB1, and its receptor TLR4. Furthermore, increased expression of the NLRP3 inflammasome and pyroptosis-related molecules (N-GSDMD, IL-1β, and IL-18) was observed. The coexistence of OSA and chronic periodontitis significantly increases the risk of cognitive dysfunction. Chronic periodontitis exacerbates hippocampal inflammation and neuronal mitochondrial damage through the HIF-1α/HMGB1/NLRP3 signaling pathway activated by OSA, leading to neuronal pyroptosis and accelerated cognitive decline. These findings provide new insights and potential strategies for preventing and treating hippocampal neuronal injury and cognitive dysfunction associated with OSA.