Tooth Loss-Associated Mechanisms That Negatively Affect Cognitive Function: A Systematic Review of Animal Experiments Based on Occlusal Support Loss and Cognitive Impairment

Abstract

BackgroundThere is a dose-response relationship between tooth loss and cognitive impairment, while tooth loss can be an independent risk factor for Alzheimer's disease (AD) and vascular dementia (VaD). Tooth loss can also accelerate nerve damage and neurodegeneration. However, the associated mechanisms remain poorly understood.ObjectiveTo conduct a systematic review of animal experiments on cognitive decline caused by the loss of occlusal support performed over the past 10 years and summarize the possible underlying mechanisms.Methods“Tooth Loss,” “Edentulous,” “Tooth Extraction and Memory Loss,” “Cognition Impairment,” and “Dementia” were used as keywords to search PubMed, Embase, SCI, ScienceDirect, and OpenGrey. A total of 1,317 related articles from 2010 to 2021 were retrieved, 26 of which were included in the review after screening according to predetermined inclusion and exclusion criteria. Comprehensiveness was evaluated using ARRIVE guidelines and the risk of bias was assessed using SYCLE'S risk of bias tool.ResultsThe putative mechanisms underlying the cognitive impairment resulting from the loss of occlusal support are as follows: (1) The mechanical pathway, whereby tooth loss leads to masticatory motor system functional disorders. Masticatory organ activity and cerebral blood flow decrease. With reduced afferent stimulation of peripheral receptors (such as in the periodontal membrane) the strength of the connections between neural pathways is decreased, and the corresponding brain regions degenerate; (2) the aggravation pathway, in which tooth loss aggravates existing neurodegenerative changes. Tooth loss can accelerates nerve damage through apoptosis and mitochondrial autophagy, increases amyloid deposition in the brain; and (3) the long-term inflammatory stress pathway, which involves metabolic disorders, microbial-gut-brain axis, the activation of microglia and astrocytes, and inflammatory cascade effect in central nervous system.ConclusionThe loss of occlusal support may lead to cognitive dysfunction through the reduction of chewing-related stimuli, aggravation of nerve damage, and long-term inflammatory stress.

Periodontal health, cognitive decline, and dementia: A systematic review and meta‐analysis of longitudinal studies

“…Tooth loss may also independently impair cognition by reducing sensorimotor stimulation from masticatory apparatus which has been linked to atrophic brain changes. This association might depend on factors like magnitude/dose and length of exposure 25,84 . An insight into this possible dose‐dependent effect is provided by our finding of somewhat higher ORs/HRs for complete versus partial tooth loss.…”

“…This association might depend on factors like magnitude/ dose and length of exposure. 25,84 An insight into this possible dose-dependent effect is provided by our finding of somewhat higher ORs/HRs for complete versus partial tooth loss. Furthermore, non-traumatic/non-surgical causes of tooth loss (e.g., dental caries and periodontitis) lead to gradual and progressive tooth loss over decades.…”

Molar loss further exacerbates 2-VO-induced cognitive impairment associated with the activation of p38MAPK/NFκB pathway

“…The oral and maxillofacial system is responsible for physiological functions, such as chewing, swallowing, and speaking. An increasing number of relevant literature have manifested that molar loss affects cognitive function and is associated with dementia (Wang et al, 2022).…”

“…The oral and maxillofacial system is responsible for physiological functions, such as chewing, swallowing, and speaking. An increasing number of relevant literature have manifested that molar loss affects cognitive function and is associated with dementia ( Wang et al, 2022 ). The deterioration of their dental health was significantly increased in clinical dementia individuals ( Okamoto et al, 2010 ; Cerutti-Kopplin et al, 2016 ; Orr et al, 2020 ).…”

The Sedentary Lifestyle and Masticatory Dysfunction: Time to Review the Contribution to Age-Associated Cognitive Decline and Astrocyte Morphotypes in the Dentate Gyrus

“…The synaptic changes in form, function, and plasticity associated with learning and memory formation are interrelated in the hippocampus [ 124 , 125 , 126 ]. As the hippocampal circuits mature, the establishment of synaptic reinforcement occurs in association with lasting structural changes and long-term potentiation (LTP).…”