Effects of tooth loss on behavioral and psychological symptoms of dementia in app knock-in mice

Abstract

ObjectivesMany patients with Alzheimer's disease (AD) experience behavioral and psychological symptoms of dementia (BPSD), which significantly affect their quality of life. It is known that 5-Hydroxytryptamine (5-HT) plays a crucial role in the development of BPSD. While the relationship between tooth loss and AD symptoms has been acknowledged, the aspect of aggression has not been focused on until now. Despite the established importance of 5-HT in BPSD, how tooth loss is related to the exacerbation of AD symptoms, especially in terms of aggression, remains largely unexplored. Although nutritional status is known to influence the progression of dementia, the specific effect of tooth loss on peripheral symptoms, notably aggression, is not well understood. MethodsIn our study, we conducted maxillary molar extractions in aged C57BL/6J and AppNL-G-F mice and observed their condition over a 3-month period. During this time, we documented significant behavioral and genetic differences between mice in the control groups and mice that underwent tooth extraction. Notably, mice that underwent tooth extraction exhibited a considerable decline in cognitive function and increased in aggression 3 months after tooth extraction compared with the control groups (C57BL/6J and AppNL-G-Fmice). ResultsOur findings suggest that molar loss may lead to reduced 5-HT levels in the hippocampus, possibly mediated by the trigeminal nerve, contributing to the development of aggression and BPSD in AD. ConclusionThis study sheds light on the intricate relationships between oral health, 5-HT, and AD symptoms, offering valuable insights into potential therapeutic avenues for managing BPSD in patients with dementia.