In an article titled Dental Deafferentation and Brain Damage: A Review and Hypothesis, published in The Kaohsiung Journal of Medicine and written by Yi-Tai Jou, the author describes masticatory function as a symphony orchestra. When all members of the symphony are present and playing well, it is a beautiful harmony.
However, if one musician, for example, is missing, it can be detrimental to the harmony of the symphony. The same is true for eating and mastication. Eating and mastication encompass all five senses. Losing a tooth can be compared to the loss of a musician in the orchestra. This can increase mental and physical stress. To cope with this added stress, cortical sensory and motor function must reorganize. This can lead to damage of cortical networks, particularly in the elderly, who may have reduced ability for reorganization.
The comparison of mastication and a symphony orchestra is a perfect assessment when considering the connection between masticatory function and cognitive function. Many studies have shown a connection with mastication and the hippocampus. The hippocampus plays an important role in the limbic system; specifically, it is responsible for processing long-term memory and emotional responses.
Animal studies using neuroimaging have suggested that masticatory dysfunction, due to soft diets or tooth loss, induced spatial memory, and learning deficits. The studies suggest this is due to the structural and functional reorganization of the hippocampus.1 In the past, it was thought that functional and structural plasticity (e.g., neurogenesis) was limited to development. New research has shown that the hippocampus maintains this plasticity throughout an individual’s entire life.2,3 Unfortunately, neurogenesis is suppressed in individuals with tooth loss. It is suggested that tooth loss initiates a stress response releasing the hormone, corticosterone. This stress hormone activates neurological alterations in the hippocampus.4
Several epidemiological studies showed dementia worsening in individuals that lost residual teeth, had an inadequate prosthesis, and decrease in biting force.1 A longitudinal study conducted in Japan seems to confirm these results concluding, “tooth loss is associated with increased risks of all-cause dementia and Alzheimer’s disease in the Japanese population.”5
Chewing State of Mind
Recorded studies of chewing and its association with cognitive function date back as far as 1939 with H.L. Hollingsworth’s study titled Chewing as a Technique of Relaxation. In this study, Hollingsworth concluded that workers were more relaxed when chewing. Since then, scientists and researchers have provided information regarding what happens in our brains when we chew, and it is fascinating.
When chewing, sensations are detected in sensory neurons, and these sensory neurons send the sensory input from the oral cavity to the central nervous system via the trigeminal ganglion and mesencephalic trigeminal nucleus. The mesencephalic neurons have fibers that extend into the brainstem reticular formation. This regulates sensory input through the reticular activating system (RAS). RAS is a web-like bundle of nerves that filters out unnecessary information; it is necessary to commit learning to memory. This mechanism of perception of the oral cavity is thought to influence memory and learning ability.6
Several different growth factors are produced in the salivary gland during mastication. Occlusal dysfunction may alter levels produced, causing an increase in the production of corticosterone. Increased production of corticosterone suppresses that action of neurons and reduces the number of neurons in the hippocampus, leading to the death of neurons.
Brain Favors Your Natural Teeth?
Mastication with natural teeth has been shown via positron emissions tomography (PET) to increase metabolic activity which leads to increased blood flow to the brain and oral tissues. Another study using functional magnetic resonance imaging showed increased brain activity upon mastication in several different regions including the primary motor cortex, primary somatosensory cortex, premotor area, supplementary motor area, insula, prefrontal cortex, thalamus, posterior parietal cortex, cerebellum, and striatum. This indicates that mastication has an influence on the hippocampus via multiple different neural pathways.6,7
Clearly, there seems to be a relationship with mastication and brain function, but what exactly happens in the brain when tooth loss causes mastication dysfunction?
Several animal studies have explained the process; however, data to explain the mechanism or lack thereof in humans is lacking. For that reason, more studies on humans are necessary to confirm the association extrapolated from animal studies. In animals, there is a clear difference in brain function when mastication is altered. When multiple teeth are missing in animal models, it becomes necessary to rewire, remap, and rebuild motor and sensory neuromuscular pathways. This can lead to non-ideal connections which can accumulate higher levels of beta-amyloid, the main component of the amyloid plaques found in the brains of patients with Alzheimer’s disease.6
In a meta-analysis assessing multiple studies on masticatory dysfunction and cognitive dysfunction, the authors found that the location of missing teeth could play a role in the loss of cognitive function. Loss of posterior teeth was far more prevalent than loss of anterior teeth, which leads to the question of whether missing anterior teeth cause the same concern when considering cognitive function?8 I certainly hope to see more studies addressing this question.
We all know there are times that extracting a tooth is unavoidable. Which may seem concerning after reading the possible cognitive effects tooth loss may have. However, the good news is that replacing missing teeth has been shown to improve cognitive function.9 In a pilot study, a comparative evaluation of brain activity and cognitive function showed an increase of 6.4 points on the Mini-mental State Exam (MMSE) in patients with an implant-retained overdenture. Though a score between 20-24 indicates mild dementia, it is an improvement when considering a score of 13-20 suggests moderate dementia. For comparison’s sake, the maximum score on the MMSE is 30.10
These studies are giving dental professionals just one more reason to encourage patients to take care of their teeth and maintain a full, healthy dentition for life. It also highlights the importance of discussing options to replace missing teeth, a very important conversation to have with patients. Not only are missing teeth a concern in the context of the above studies, but missing teeth also contribute to poor nutrition which is also associated with cognitive decline. The oral-systemic link never ceases to amaze me. Dental professionals play an integral role in systemic health; we can and do change lives.
- Chen, H., Iinuma, M., Onozuka, M., Kubo, K. Chewing Maintains Hippocampus-Dependent Cognitive Function. Int J Med Sci. 2015; 12(6): 502-509. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466515/
- Leuner, B., Gould, E. Structural Plasticity and Hippocampus Function. Annu Rev Psychol. 2010; 61: 111-C3. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012424/
- Bettio, L.E.B., Rajendran, L., Gil-Mohapel, J. The effects of Aging in the Hippocampus and Cognitive Decline. Neurosci Biobehav Rev. 2017 Aug; 79: 66-86. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28476525
- Kubo, K.Y., Murabayashi, C., Kotachi, M., Suzuki, A., Mori, D., Sato, Y., Onozuka, M., Azuma, K., Iinuma, M. Tooth Loss Early in Life Suppresses Neurogenesis and Synaptophysin Expression in the Hippocampus and Impairs Learning in Mice. Arch Oral Biol. 2017 Feb; 74: 21-27. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27846401
- Takeuchi, K., Ohara, T. Furuta, M., Takeshita, T., Shibata, Y., Hata, J., Yoshida, D., Yamashita, Y., Ninomiya, T. Tooth Loss and Risk of Dementia in the Community: the Hisayama Study. J Am Geriatr Soc. 2017 May;65(5): 95-100. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28272750
- Krishnamoorthy, G., Al, N., Balkrishanan, D. Mastication as a Tool to Prevent Cognitive Dysfunction. Jpn Dent Sci Rev. 2018 Nov; 54(4): 169-173. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175965/
- Onozuka, M., Fujita, M., Watanabe, K., Hirano, Y., Niwa, M., Nishiyama, K., Saito, S. Mapping Brain Region Activity During Chewing: A Functional Magnetic Resonance Imaging Study. J Dent Res. 2002 Nov; 81(11): 743-746. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/12407087
- Alvarenga, M.O.P., Ferreira, R.O., Magno, M.B., Fagundes, N.C.F., Maia, L.C., Lima, R.R. Masticatory Dysfunction by Extensive Tooth Loss as a Risk Factor for Cognitive Deficit: A Systematic Review and Meta-Analysis. Front Physiol. 2019 Jul 3; 10: 832. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618904/
- De Cicco, V., Barresi, M., Fantozzi, M.P.T., Cataldo, E., Parisi, V., Manzoni, D. Oral Implant-Prosthesis: New Teeth for a Brighter Brain. PloS One. 2016; 11(2): e0148715. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771091/
- Banu RF, Veeravalli PT, Kumar VA. Comparative Evaluation of Changes in Brain Activity and Cognitive Function of Edentulous Patients, with Dentures and Two-Implant Supported Mandibular Overdenture-Pilot Study. Clin Implant Dent Relat Res. 2016 Jun; 18(3): 580-7. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25825258