Review Article

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Edentulism (missing teeth) and brain central nervous system (CNS)

deafferentation: a narrative review
Dani Stanbouly1, Qingcong Zeng2, Yi-Tai Jou3,4, Sung-Kiang Chuang5,6,7,8
1
Dental Student, College of Dental Medicine, Columbia University, New York, NY, USA; 2Department of Oral and Maxillofacial Surgery, University
of Alabama at Birmingham School of Dentistry, Birmingham, AL, USA; 3Robert Schattner Center, Department of Endodontics, School of Dental
Medicine, University of Pennsylvania, Philadelphia, PA, USA; 4Department of Endodontics, Kaohsiung Medical University, School of Dentistry,
Kaohsiung; 5Department of Oral and Maxillofacial Surgery, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA, USA; 6Private
Practice, Brockton Oral and Maxillofacial Surgery Inc., Brockton, MA, USA; 7Department of Oral and Maxillofacial Surgery, Good Samaritan
Medical Center, Brockton, MA, USA; 8Department of Oral and Maxillofacial Surgery, Kaohsiung Medical University, School of Dentistry, Kaohsiung
Contributions: (I) Conception and design: SK Chuang; (II) Administrative support: SK Chuang; (III) Provision of study materials or patients: All
authors; (IV) Collection and assembly of data: D Stanbouly; (V) Data analysis and interpretation: D Stanbouly; (VI) Manuscript writing: All authors;
(VII) Final approval of manuscript: All authors.
Correspondence to: Sung-Kiang Chuang, DMD, MD, DMSc. Department of Oral and Maxillofacial Surgery, University of Pennsylvania, School of
Dental Medicine, Philadelphia, PA, USA. Email: [email protected].

Background and Objective: Edentulism is a major public health issue that poses plenty of systemic
health ramifications. The absence of teeth impairs an individual’s ability to speak and alters their facial
aesthetics negatively. Moreover, edentulism undermines the ability to adequately chew food, particularly
those with firmer textures, which are often nutrient-dense fruits and vegetables. Nevertheless, the dental
deafferentation (DD) that characterize tooth loss and its deleterious impact on the brain is a budding
paradigm. The objective of this narrative review is to explore the effects of edentulism on the central nervous
system (CNS) via the process of deafferentation.
Methods: We reviewed the literature from 1985 to 2021 to identify all relevant studies published regardless
of study design across PubMed. Studies in languages other than English were excluded.
Key Content and Findings: The process of DD secondary to tooth loss eliminates several peripheral
afferent neural inputs, which can cause central reorganization of the sensory and motor cortices.
Adequate mastication with complete dentition reinforces such neural functional streams. As such, DD
and the resulting, impaired mastication forces the brain to undergo neuroplastic changes, which are often
accompanied by detrimental effects. When the DD impacts neural networks associated with the facial and
vestibulocochlear nerves, taste and hearing deficits may result respectively. Cognitive decline may follow DD
and edentulism—the impaired cerebral blood flow that follows suboptimal mastication, the poor, nutrient-
sparse diets of edentulous individuals, and the chronic inflammation associated with periodontitis among
edentulous individuals are the key mechanisms behind this link. The neural stresses imposed by DD and
edentulism in excess can damage the brain to an extent enough to trigger Alzheimer’s disease (AD).
Conclusions: The neural implications edentulism on the brain are vast, from sensory deficits to cognitive
decline, extending far beyond facial aesthetics and ability to chew. The neural interconnectedness among the
teeth, mastication, and the brain suggest novel interventions that can be taken to promote brain health and
prevent the exacerbation of neurodegenerative disease.

Keywords: Edentulism; mastication; dental deafferentation (DD); central nervous system (CNS)

Received: 27 November 2021; Accepted: 16 May 2022; Published online: 06 June 2022.
doi: 10.21037/fomm-21-117
View this article at: https://dx.doi.org/10.21037/fomm-21-117

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Page 2 of 8 Frontiers of Oral and Maxillofacial Medicine, 2024

Introduction associated with hypertension amongst post-menopausal

women. The authors determined that subjects with missing
Edentulism is the unconditional and irreversible state of
teeth had significantly higher diastolic blood pressure
losing all natural (i.e., permanent) teeth. Deemed the dental
relative to subjects without missing teeth. After controlling
equivalent of mortality—the terminus of periodontal disease
for covariates (i.e., obesity, hypercholesterolemia, and
and dental caries, edentulism is certainly a major public health
hypertriglyceridemia), subjects with missing teeth were
issue (1). The incidence of edentulism is higher among certain
3.59 times more likely to have hypertension relative to
populations: older, poor female individuals with a high school
subjects without missing teeth. The authors believed this
education or less who smoke. This is relative to wealthier,
eventual result was largely due to a disparity in diet between
male individuals with a higher level of education who do not
the two study groups—subjects with missing teeth had
smoke (2,3). Additionally, arthritis, asthma, diabetes, and
decreased levels of vitamin C, an antioxidant (10). Further,
insufficient visits/access to a dental center were independently
abundant intake of heavily processed fat and carbohydrate-
associated a decreased incidence of edentulism (4,5).
rich foods lead to obesity and obesity-related diseases, such
A testament to advances in preventative dentistry, as insulin resistance and diabetes (7).
edentulism has fortunately been on a steady decline over Further, edentulous individuals electively avoid partaking
the years. From 18.9% in 1957–1958, the prevalence in social activities due to the feelings of shame they could
of edentulism significantly declined to a trivial 4.9% in experience due to their facial appearance and impaired
2009–2012 (6). This decline was particularly marked among speaking ability. Igarashi et al. quantified the impact of tooth
the more affluent households. Further, this decline appears loss on an individual’s social life. The authors conducted a cross-
to persist over the upcoming years. In a study that utilized sectional study to determine whether vision, hearing and tooth
data five national cross-sectional health surveys, Slade loss were linked to decreased social interaction, which was
et al. project that the prevalence of edentulism will reach defined as ‘not meeting my friends’. Igarashi et al. determined
as low as 2.6% by the year 2050—this continual decline that tooth loss, after adjusting for confounders, was associated
is, however, counteracted by the ever increasing world with an increased risk of decreased social interaction (11).
population, especially the elderly subpopulation, who are This self-imposed social handicap that edentulism imparts
more likely to be edentulous (6). on the individual jeopardizes his/her mental health, self-
The health ramifications of edentulism are plenty. esteem, and wellbeing, psychologically predisposing him/
More evidently, edentulism worsens an individual’s facial her to hopelessness and depression (5). In a qualitative study
appearance as well as several basic functions, such as on 50 edentulous individuals, Fiske et al. determined that
the ability to eat and speak. Compromised mastication denture wearers have reduced self-confidence, premature
causes individuals to avoid fruits and vegetables, which aging, altered self-image, insecurity over their prothesis, and
are nutrient-dense foods. Reduced fiber intake can incite diminished capacity to form close relationships (12).
chronic inflammation of the gastric mucosa, peptic or A newly hypothesized paradigm of health ramifications
duodenal ulcers, and even upper gastrointestinal and secondary to edentulism entails the central nervous system
pancreatic cancer (7). (CNS). At the University of Pennsylvania School of Dental
Ndegwa et al. conducted a prospective cohort study to Medicine, Dr. Jou discussed the different means by which
determine whether an association existed between oral a process known as dental deafferentation (DD) damages
health and gastric cancer. The authors determined that the brain. In this article, we shall focus on the effects of
subjects with fewest teeth at baseline had an increased edentulism on the process of deafferentation, particularly on
risk of gastric cancer at follow-up relative to those with all the CNS. We shall explore the latest research that has been
examined teeth present This risk was greatest amongst the conducted on different aspects of this rather novel paradigm
youngest age group and diminishes with older age groups (8). in oral and maxillofacial medicine. We aim to identify the
In the same vein, another prospective cohort study different mechanisms by which a diseased stomatognathic
determined that tooth loss was associated with increased system affects contributes to cognitive decline [e.g.,
risk of gastric non-cardia cancer (9). Alzheimer’s disease (AD)] and neurodegenerative diseases.
Insufficient antioxidants can warrant the development We reviewed the literature to identify all studies published thus
of cardiovascular disease (7). Taguchi et al. conducted a far regardless of study design across multiple databases. We
cross-sectional study to determine whether tooth loss was present this article in accordance with the Narrative Review

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Frontiers of Oral and Maxillofacial Medicine, 2024 Page 3 of 8

Table 1 The search strategy summary

Items Specification

Date of search 08/01/2021–11/01/2021

Databases and other sources searched PubMed

Search terms used Edentulism; tooth loss; dental deafferentation; edentulism and CNS damage; edentulism and
cognitive; edentulism and senses

Timeframe 1985–2021

Inclusion and exclusion criteria Inclusion criteria consisted of articles written in English that addressed the topic at hand. No
particular study type was preferred. Excluded articles written in languages other than English

Selection process The selection process was independently conducted by Dani Stanbouly
CNS, central nervous system.

reporting checklist (available at https://fomm.amegroups.com/ fibers, proprioceptive receptors, and mechanoreceptors.

article/view/10.21037/fomm-21-117/rc). Functional aspects of the dentition that are lost include
interdental coordination between adjacent teeth as well as
interarch relationships where the opposing arch no longer
Methods
completes the masticatory function (14).
A narrative review was conducted to achieve the aims of the Impaired mastication secondary to multiple tooth loss has
following study. PubMed was queried to identify all relevant been shown to influence several neurologic processes. The
articles. To enable a more comprehensive review, the process of mastication, with a healthy dentition, exercises
inclusion criteria was not limited to a specific study design. many cortical regions of the brain, including but not limited
Consistent with others (13), the authors also did not deem to primary somatosensory cortex (SI) and the primary motor
it necessary to critique the selected articles. The selection cortex (MI). Onozuka et al. conducted a functional magnetic
process was conducted by author D.S. using the following resonance imaging (fMRI) study to explore the relationship
terms: edentulism; tooth loss; dental deafferentation; between chewing and brain regional activity in 17 subjects.
edentulism and CNS damage; edentulism and cognitive; The authors determined that chewing increased blood
edentulism and senses. Additionally, the references within oxygenation level-dependent (BOLD) signals specifically
the selected articles were screened to determine any more in the sensorimotor cortex, supplementary motor area
relevant articles that could supplement the review (Table 1). (SMA), insula, thalamus, and cerebellum (15). Takahashi
et al. attempted to identify which cerebral areas are involved
in mastication with changes in food hardness. The authors
What is DD?
determined that there were selective activations of the
DD is the process by which peripheral afferent neural inputs SMA, dorsolateral prefrontal cortex (DLPFC), and superior
are eliminated in relation to dental and masticatory apparatuses. temporal gyrus (STG) of the left hemisphere, and the
Tooth loss, local and/or generalized periodontal detachment, premotor area (PM) and inferior parietal lobule (IPL) of
inadequate operative or prosthetic restorations, and orthodontic the right hemisphere as the hardness of chewing gum varied
managements are all examples of DD. No correlation between widely in oral cavity during mastication (16).
DD and markers of brain damage has yet to be proven—the You see, our brain integrates various sensory and motor
jury is out on this hypothesis as it is put to the test (14). information associated with mastication—the sensations
The typical case of DD is tooth loss, often after experienced within the oral mucosa as well as the operations
exodontia. Other dental treatments can induce DD, such as of the masticatory muscles are etched in our CNS. In so
root canal therapy (RCT). However, the resultant DD from doing, our brain renders eating an effortless and pleasurable
RCT differs from that in tooth loss. Unlike RCT, tooth habit. Thus, several neurological complications secondary
loss from exodontia rids the dentition of various structural to edentulism have been hypothesized and studied on the
and functional aspects. Structural components that are premise of the vital role mastication plays in the brain and
lost after exodontia include the transeptal fibers, Sharpey’s its cerebral activity (14).

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Page 4 of 8 Frontiers of Oral and Maxillofacial Medicine, 2024

DD and the senses diseases, such as hearing impairment (24). It has also been
proposed that the reduced vertical dimension of occlusion
Taste and olfaction can progressively weaken with DD
amongst edentulous patients impacts ear canal resonance
and impaired mastication (17-19). Utsugi et al. sought to
and hearing (22). Peeters et al. sought to explore the extent
assess the effects of mastication on neurogenesis at the
to which hearing ability varied across the number of teeth
accessory olfactory bulb (AOB) and pheromonal responses.
and/or the number of occluding tooth pairs. Subjects were
The authors determined that soft diet-fed rats exhibited
classified according into four groups: (I) complete dentures
decreased neurogenesis at the AOB relative to hard diet-
wearers in both jaws; (II) shortened dental arches; (III)
fed rats. The number of synthesized bromodeoxyuridine-
full dental arches in both jaws; (IV) no occlusal stops (i.e.,
immunoreactive (BrdU-ir) cells at the caudal half of the
no occlusal vertical dimension). The authors determined
AOB was significantly lower in mice fed soft diets relative
that both air and bone conduction was significantly worse
to mice fed hard diets. Regarding phermonal responses,
for subjects without vertical occlusion relative to the three
the numbers of Fos-ir cells in the rostral and caudal halves
other groups. Because edentulous subjects without occlusal
of the AOB were lower in mice fed soft diets months than
those of mice fed hard diet after four months (18). stops had worse hearing loss relative to edentulous subjects
Another study by Boucher et al. determined that with complete dentures, Peeters et al. believes that it is the
impaired mastication in the context of DDs from RCT loss of vertical dimension that influences hearing loss (23).
therapy can caused taste deficits. The authors compared Finally, the low bone mineral density that characterizes
electrogustometric (taste) threshold among six study periodontal disease, the terminal stage of which is
groups designated according to the number DD teeth— edentulism, may be the culprit behind the resulting hearing
that is, extracted teeth or teeth treated with RCT. Subjects impairment. The demineralization is believed to systemically
with more than seven deafferented teeth had significantly pervade the aspect of the temporal bone that encapsulates
higher taste thresholds than subjects with less than seven the cochlea (24). A cross-sectional study on postmenopausal
deafferented teeth (17). Korean women showed that low bone mineral density was a
Another sense that is affected by DD and impaired risk factor for hearing impairment (25).
mastication is hearing (20-24). Lawrence et al. investigated
whether an association existed between tooth loss and DD and cognitive decline
hearing acuity or not in a 20-year longitudinal study. The
authors determined that subjects who went from having Tooth loss and impaired mastication also have deleterious
greater than 17 teeth at baseline to less than 17 teeth at effects on cognition (26-34).
follow were more than 1.6 times more likely to suffer A 13-year longitudinal study investigating the association
hearing decline relative to those with no change in their between the number of existing teeth and cognitive decline
dentition. Further, every tooth lost since baseline resulted in China revealed the importance of a health dentition
in 1.04-fold odds of acquiring hearing decline relative to a as a requisite to a healthy mind. By Mini-Mental Status
stagnant dentition (21). In a cross-sectional study on 1,004 Examination (MMSE), subjects expectedly illustrated
subjects aged 36 to 84 years in Japan, Tanaka et al. found cognitive decline with age. That being said, possessing a
that higher number of teeth is associated with decreased greater number of teeth significantly stalled the rate of
prevalence of hearing impairment. After adjusting for cognitive decline (26). Another study conducted in Ecuador
covariates, the authors determined that subjects with 26 ended up with similar results. The subjects were classified
to 27 teeth, and 22 to 25 teeth were 1.4 and 1.5 times according to whether they had severe edentulism (less than
respectively more likely to suffer from hearing impairment 10 teeth) or not. Cognitive functioning was gauged using the
relatively to subjects with 28 teeth. Most notably, having Montreal Cognitive Assessment (MoCA). After controlling
less than 22 teeth imposed a 1.9-fold risk of developing for various cofactors, including dementia, MoCA scores
hearing impairment (24). among subjects with severe edentulism were significantly
Several mechanisms are believed to underly the link lower than those without severe edentulism (31).
between DD and hearing impairment. Deafferentation of A cross-sectional study by Avlund et al. sought to determine
the stomatognathic system can have systemic implications whether cognitive function was related to oral disease in the
in the brain, restructuring sensory and motor cortices. This elderly—159 individuals over the age of 80 were dentally
reactive process can trigger and aggravate neurodegenerative and cognitively examined. Individuals with low cognitive

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Frontiers of Oral and Maxillofacial Medicine, 2024 Page 5 of 8

exam score were four times more likely to neglect regular Firstly, the process of mastication with adequate dentition
professional dental care. They also had a higher risk of stimulates cerebral blood flow, activates cortical areas,
coronal caries than individuals with higher cognitive exam and increases blood oxygen levels (41,42). A systematic
scores (27). review that explored the protective role of mastication
The results of Avlund et al. were replicated in another against cognitive decline revealed that mastication greatly
study that investigated the reciprocal relationship between activated the frontotemporal cortex, the caudate nucleus,
cognitive function and edentulism among individuals aged and the thalamus. Further, partially edentulous participants
45 or older. A total of 17,076 respondents participated in exhibited significant deactivation of the prefrontal cortex
the baseline surveys that determined cognitive function when they chewed without a prosthesis. This systematic
and edentulism. At follow-up 4 years later, 14,038 subjects review also illustrated a positive association between
from the original sample responded to the same survey. mastication and in regional cerebral blood flow. As such,
Interestingly, the impact of edentulism at baseline led to the authors concluded that mastication may be protective in
significantly lower levels of cognitive function at follow-up patients with cognition impairment and neurodegenerative
amongst the elderly (60 or older). This was not the same for diseases (43). Hence, impaired mastication in the case
individuals aged 45–59 (29). of edentulism compromises the aforementioned vital
The most severe cognitive complication that is associated processes.
with edentulism is AD (35-38). Dioguardi et al. conducted Another mechanism that potentially underlies the
a meta-analysis investigating the association been tooth loss association between edentulism and AD concerns nutrition.
and AD. Qualitative analysis of the eligible studies revealed As was discussed earlier, edentulism can markedly influence
that, relative to patients without AD, patients with AD were an individual’s diet. Nutrient dense foods, such as fruits
1.5 times more likely to develop tooth loss and 2.3 times and vegetables often have rigid textures that necessitate
more likely to wind up edentulous. However, the converse adequate dentition. In contrast, processed foods often have
is not true. The mechanism behind this causal relationship, delicate textures that are easy to chew. Hence, individuals
the authors believe is the memory impairment that with a declining number of teeth progressively substitute
accompanies AD: afflicted patients unintentionally neglect nutrient dense foods for processed foods. Many studies
their dental hygiene, which leads to the corresponding have articulated the link between poor oral health and
tooth loss and edentulism (35). This mechanism has malnutrition (44-46). Ioannidou et al. determined that
been supported by study investigating the relationship tooth loss strongly associates with malnutrition among
between tooth loss and cognitive function. Avlund et al. sufferers of chronic kidney disease. The authors classified
determined that individuals with low cognition were five the patients into five groups according to their dentition
times more likely to not use dental services regularly (27). as follows: group 0 = complete natural dentition; group 1 =
That being said, a prospective cohort study by Takeuchi et complete mixed dentition (natural teeth and replaced teeth);
al. that illustrated the added risk of incurring AD amongst group 2 = incomplete (natural or mixed) dentition; group
edentulous patients, was acknowledged and elaborated 3 = fully edentulous with full dentures; and group 4 = fully
upon in the meta-analysis. The authors determined that edentulous with no dentures. The rate of individuals who
an inverse association between the number of remaining had a low protein intake of <1.2 g/kg/day was significantly
teeth and risk of incurring AD. Further, after controlling different among the five groups, being highest among
for all potential confounders, the authors determined that group 4 (13.9%)—this rate was much greater than the rest
patients with 10 to 19 teeth, patients with one to nine teeth, of the groups (group 3, 2.0%; group 2, 1.3%; group 1, 1.0%;
and edentulous were 1.6, 1.8, and 1.6 times more likely to group 0, 1.3%). The same trend followed for fraction of
incur all-cause dementia relative to patients with 20 teeth individuals who had a low caloric intake of <30 Kcal/kg/day.
or more (39). Even more, the number of teeth was shown Further, for every five teeth lost, patients were 1.42 times
to be associated with the extent of gray matter atrophy, more likely to have a low protein intake of <1.2 g/kg/day
further supporting the paradigm of edentulism as a proxy and 1.38 times more likely to have a low caloric intake of
for dementia and its progress (40). <30 Kcal/kg/day (44).
Takeuchi et al. purported several mechanisms for this Cognitive ramifications follow a poor diet. Several
association between edentulism, most of which are identical studies have illustrated the link between nutrition and
to those concerning edentulism and cognitive function. cognitive decline or AD (47,48). Tucker et al. investigated

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Page 6 of 8 Frontiers of Oral and Maxillofacial Medicine, 2024

whether a low serum vitamin B level predicted cognitive vitality of healthy dentition and functional mastication. The
decline in aging men. Serum levels of the relevant vitamins issues of edentulism are more profound than previously
were determined among 321 subjects, of whom the mean thought, extending far beyond facial aesthetics and ability
age was 67. Cognitive testing that assessed working to chew. The neural interconnectedness among the teeth,
memory (backward digit span), recall (word list memory the action of eating, and the brain exhibited by recent
test), language (verbal fluency), and spatial copying investigations suggest novel interventions that can be taken
(constructional praxis) was conducted at baseline and to promote brain health and prevent the exacerbation
3 years later. The authors determined that constructional of neurodegenerative disease. A perfect smile should be
praxis score (i.e., ability to spatially manipulate designs deemed a marker of brain health to a similar magnitude as it
and patterns) was positively associated with serum levels of is deemed a marker of oral health.
folate and vitamins B-6 and B-12 and negatively associated
with serum levels of homocysteine. Constructional praxis
Acknowledgments
scores were also negatively associated with dietary intake
of folate and vitamins B-6 and B-12 at baseline. Further, Funding: None.
Homocysteine was significantly negatively associated with
recall memory scores. Homocysteine, an amino acid that
Footnote
is elevated in the presence of insufficient serum levels of
folate, vitamin B-12, or vitamin B-6 (49). Reporting Checklist: The authors have completed the
The final mechanism that was put forth by Takeuchi et al. Narrative Review reporting checklist. Available at https://
was discussed earlier: the impact of chronic inflammation on fomm.amegroups.com/article/view/10.21037/fomm-21-
the onset and progression of dementia. A common cause of 117/rc
tooth loss and edentulism, periodontitis transpires through
both local and a systemic inflammation marked by the rise Conflicts of Interest: All authors have completed the ICMJE
of several cytokines, such as interleukin-1, interleukin-6, uniform disclosure form (available at https://fomm.
C-reactive protein (CRP), and tumor necrosis factor alpha amegroups.com/article/view/10.21037/fomm-21-117/
(TNF-α) (50). Systemic inflammation, per se, has been coif). SKC serves as an unpaid editorial board member of
shown to be associated with cognitive decline. Holmes et Frontiers of Oral and Maxillofacial Medicine from July 2020 to
al conducted a prospective study investigating the effect June 2024. The other authors have no conflicts of interest
of systemic inflammation on the progression of AD. The to declare.
study entailed three-hundred subjects with mild to severe
AD who were administered blood tests to measure the level Ethical Statement: The authors are accountable for all
systemic inflammatory markers, namely TNF-α, at baseline, aspects of the work in ensuring that questions related
two months later, four months later, and six months later. to the accuracy or integrity of any part of the work are
Further, caregivers of subjects were interviewed to identify appropriately investigated and resolved.
whether the subjects experienced incidents of systemic
inflammatory event, which was defined as a transient Open Access Statement: This is an Open Access article
infection or trauma separate from the CNS with a minimum distributed in accordance with the Creative Commons
consequent serum CRP level of 1 μg/mL. High levels of Attribution-NonCommercial-NoDerivs 4.0 International
TNF-α at baseline increased the rate of cognitive decline by License (CC BY-NC-ND 4.0), which permits the non-
four times. In contrast, subjects who had low levels of serum commercial replication and distribution of the article with
TNF-α throughout the study exhibited no cognitive decline the strict proviso that no changes or edits are made and the
at the 6-month follow-up (51). original work is properly cited (including links to both the
formal publication through the relevant DOI and the license).
See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
Conclusions

The neural implications of DD and edentulism on the

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doi: 10.21037/fomm-21-117
Cite this article as: Stanbouly D, Zeng Q, Jou YT, Chuang
SK. Edentulism (missing teeth) and brain central nervous
system (CNS) deafferentation: a narrative review. Front Oral
Maxillofac Med 2024;6:8.

© Frontiers of Oral and Maxillofacial Medicine. All rights reserved. Front Oral Maxillofac Med 2024;6:8 | https://dx.doi.org/10.21037/fomm-21-117