Restoration of Normal Occlusion Suppresses the Risk of Dementia.

Tooth loss is associated with a progressive decline in cognitive ability. Although occlusal support after tooth loss using dentures may reverse this effect, the underlying mechanisms are unclear, hampering improved evidence-based dentistry for at-risk patients. The current experiments examined the associations of tooth loss and restoration of occlusal support with neuropathology and cognitive decline in a mice model of Alzheimer's disease (AD). A triple-mutant knock-in mouse model of AD (AppNL-G-F mice), and a single-mutant knock-in control line, (AppNL mice), were divided into three subgroups: untreated, molar extraction at 6 weeks of age, and molar extraction with occlusal support. Animals were examined before occlusal support at 2, 4, and 6 months and after occlusal support at 3, 5, and 7 months of age. We designated 2-3, 4-5, and 6-7 months as the early, middle, and late stages. Cognitive functions were assessed using the 8-arm radial maze test and novel object recognition test, while accumulation or altered expression levels of AD-associated molecules were measured in hippocampus. The App NL-G-Fmice and AppNL mice groups showed significant cognitive decline and increased accumulation of Aβ and phosphorylated Tau in the hippocampus during the early and middle stages. Restoring normal occlusal support suppressed the upregulation of AD-related molecules, including Aβ, phosphorylated Tau, and interleukin-1β in App NL-G-F mice during the early and middle stages. Restoration of normal occlusal support can mitigate the risk factors of dementia, potentially by reducing neuroinflammation and thereby reversing Aβ and phosphorylated Tau accumulation.