Water Fluoridation and Cognitive Function: A Closer Look at the Evidence
An essay in this series1Lamster I. The effects of water fluoridation on cognitive function: The story continues. Colgate Oral Health Network, 2019. reviewed a 2019 study published in JAMA Pediatrics which reported the relationship of pregnant women’s exposure to water fluoridation to the intelligent quotient (IQ) of their children at 3 to 4 years of age2Green R, Lanphear B, Hornung R, Flora D, Martinez-Mier EA, Neufeld R, et al. Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada. JAMA Pediatr. 2019.. This study from Canada found reduced IQ in children whose mothers ingested fluoridated water during the pregnancy. This publication2Green R, Lanphear B, Hornung R, Flora D, Martinez-Mier EA, Neufeld R, et al. Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada. JAMA Pediatr. 2019. was accompanied by both a comment from the editor about publication of the controversial paper3Christakis DA. Decision to Publish Study on Maternal Fluoride Exposure During Pregnancy. JAMA Pediatr. 2019. and an invited editorial that raised a number of points about the importance of water fluoridation as a public health measure, as well as the concerns about fluoride as toxic to neurodevelopment4Bellinger DC. Is Fluoride Potentially Neurotoxic? JAMA Pediatr. 2019..
At the time of publication of the report by Green et al2Green R, Lanphear B, Hornung R, Flora D, Martinez-Mier EA, Neufeld R, et al. Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada. JAMA Pediatr. 2019., the National Toxicology Program (NTP), a component of the National Institute of Environmental Health Sciences (one of twenty-seven Institutes and Centers of the U.S. National Institutes of Health), issued a draft report reviewing the available literature examining the relationship of exposure to fluoride and cognitive development/function5NTP. 2019. Draft NTP Monograph on the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. Office of Health Assessment and Translation, Division of hte NTP, National Institute of Environmental Health Services, National Institutes of Health, US Department of Health and Human Services.. The major conclusion of the draft report was that exposure to fluoride/fluoridated water was “presumed to be a cognitive neurodevelopmental hazard to humans”. However, this draft report has subsequently been reviewed by an expert committee convened by the National Academies of Sciences, Engineering and Medicine (NAS; a non-governmental organization established in 1863 to serve as an independent advisor to the United States on scientific matters). The conclusion of the expert committee6Review of the Draft NTP Monograph: Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. The National Academies Collection: Reports funded by National Institutes of Health. Washington (DC)2020. was that the available evidence did not support the conclusions in the NAS draft report. The committee clarified their conclusion by stating that no determination could be made regarding cause and effect. The chair of the committee David Savitz stated, “we’re saying that the report doesn’t provide the trail of evidence and logic that would be desired to reach a conclusion.”
An in-depth review of the committee’s concerns7Anderson P. Experts question evidence linking fluoride to lower IQ. https://www.medscape.com/viewarticle/926346. Accessed March 9, 2020. included the draft report’s failure to 1) adequately consider the bias in the selection of studies for review. The sources of the many of the studies selected for review was the Fluoride Action Network, an anti-fluoridation organization, 2) the risk of bias associated with the referenced studies was not always included, 3) the failure to fully compare studies that used the same methodology, i.e. how fluoride exposure was measured, how neurodevelopment and intelligence were evaluated, 4) confounding, which would consider the effect of other variables, was not consistently a part of the cited studies and 5) there was no meta-analysis, which would have combined the effects of different studies, with weighting based on the sample size in each study. A meta-analysis combines the outcomes from multiple studies to answer questions by evaluating the larger total population. A properly performed meta-analysis depends upon strict inclusion/exclusion criteria when determining which studies are to be included. This assures that the conclusions are based on the findings from the most scientifically valid reports.
An important concern about the draft report is the inclusion of studies that are methodologically poor. To provide an example of a well-performed study that has addressed the water fluoridation/cognitive function linkage, a long-term study from New Zealand examined exposure to water fluoridation throughout life and IQ8Broadbent JM, Thomson WM, Ramrakha S, Moffitt TE, Zeng J, Foster Page LA, et al. Community Water Fluoridation and Intelligence: Prospective Study in New Zealand. Am J Public Health. 2015;105(1):72-6..
The longitudinal population study from New Zealand evaluated a birth cohort from 1972-1973 to determine the relationship between fluoride exposure before the age of 5 (including fluoridated water, fluoride-containing dentifrice and fluoride supplements) and intelligence (IQ) between the ages of 7 and 12 years and then at 38 years. The population were members of the Dunedin Multidisciplinary Health and Development Study, a cohort of 1037 individuals born in Dunedin, New Zealand. For this analysis, data was available from 992 individuals. The Wechsler Adult Intelligence Scale – Revised was employed during childhood, and the Wechsler Adult Intelligence Scale – fourth Edition was used when the cohort were adults. After adjustment for confounders, and comparing these two groups as children and adults, there were no differences in IQ comparing individuals who lived in areas with fluoridated water, used fluoridated toothpaste or fluoride tablets versus those individuals who did not ingest these fluorides (Table 1).
The authors make several points worth mentioning.
- The strengths of this report include the use of a well-recognized tests for IQ, the prospective nature of the study, and the length of time of follow-up.
- Limitations include the inability to determine the amount of water consumed by study participants living in areas with fluoridated water, as well as determine other dietary sources of fluoride.
- They mention that previous studies have often failed to consider the recognized differences in IQ of persons who live in different locales, i.e. higher for persons in urban versus rural areas. They suggested that this difference (including, for example, broader educational opportunities in urban settings) may account for the differences observed in some studies.
- They stated that as a group, the participants in this study are comparable to those in similar geographic settings in North America and Europe. The concentration of fluoride in the water in New Zealand is 0.7-1.0 parts per million, which is generally equivalent to what is found in most other countries that fluoridate the water supply. Dunedin has established a concentration of fluoride in water at 0.75 parts per million.
Another national study that has examined several outcomes associated with levels of fluoride in drinking water was released by the Swedish Institute for Evaluation of Labour Market and Education Policy9Aggeborn L and Ohman M. Institute for Evaluation of Labour, Market and Education Policy (Sweden). Working Paper 2017: 20.. This study was not included in the draft of the NTP report. Available data for individuals born between 1985 and 1992 were reported. Information about the concentration of fluoride in the drinking water was available, and the primary outcomes were cognitive and non-cognitive test results, scores on math tests as well as the impact of exposure to fluoride in the water on the labor market.
When discussing fluoride in the water supply, in addition to adding fluoride to municipal supply, ground water often naturally contains fluoride as a result of its passage through rock. In Sweden, the ground water is naturally fluoridated, the levels are monitored, and authorities allow the concentration to be maintained if the concentration is at or below the recommended upper level of 1.5 parts per million. They acknowledge the controversy related to fluoride exposure and adverse effects on cognitive function but point out that in a number of those studies the fluoride concentration was well above the concentration considered to be safe, and some studies suffered from methodological deficiencies.
Their analysis of the available data for the 1985 to 1992 birth cohorts includes IQ at the age of 16 (for a subset of the population), and dental outcomes in 2008 and 2013, as well as income and employment data from 2014. The fluoride exposure via the water supply was determined based on residence and national data on fluoride concentration in each region. Potential confounders were also considered in the analysis. The total population of the cohort was 825,000 persons, with subsets available for a more detailed analysis (e.g. 728,000 persons were evaluated for the important outcome of employment status).
The results were as follows.
- Exposure to water fluoridation is associated with improved dental health.
- Fluoride exposure had no effect on cognitive or non-cognitive function. Further, no differences were seen for math scores.
- Fluoride exposure was associated with an increase in annual income and being employed (versus unemployed). Their interpretation is that better dental health provides an advantage in the labor market.
The authors conclude that in terms of policy implications, especially for countries considering water fluoridation, introduction of fluoridation will have health and personal benefits. Further, if the fluoride concentration is at or below the recommended concentration, fluoridation is safe.
What are the conclusions that can be drawn from both the recent report from the NTP draft report5NTP. 2019. Draft NTP Monograph on the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. Office of Health Assessment and Translation, Division of hte NTP, National Institute of Environmental Health Services, National Institutes of Health, US Department of Health and Human Services., the NAS review of that report6Review of the Draft NTP Monograph: Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. The National Academies Collection: Reports funded by National Institutes of Health. Washington (DC)2020. and the other literature regarding the value of water fluoridation, and whether water fluoridation is toxic for neurodevelopment?
- The benefits of water fluoridation on oral and dental health are undeniable, with a robust literature that dates back 75 years10Parnell C, Whelton H, O’Mullane D. Water fluoridation. Eur Arch Paediatr Dent. 2009;10(3):141-8.. This conclusion continues to be reinforced as seen in a 2018 report from Public Health England11Public Health England. Water fluoridation. Health monitoring report for England 2018: Public Health England; 2018 [Available from: https://www.gov.uk/government/publications/water-fluoridation-health-monitoring-report-for-england-2018. Accessed April 24, 2020., which noted that five-year-old children who lived in areas with fluoridated water experienced a lower caries rate and less severe caries as compared to children in a non-fluoridated area. Benefits were seen in both affluent and less-affluent areas. In addition, the chances of requiring a hospital-based tooth extraction were significantly lower in fluoridated versus non-fluoridated areas.
- Fluoride is toxic in high concentrations, but at the optimal concentration is associated with important oral health benefits with a very low risk of complications. Drugs and compounds used to improve health have an appropriate therapeutic concentration or dose. Lower concentrations/doses have little or no effect and higher concentrations/doses can have detrimental effects, leading to morbidity and even mortality. However, the primary detrimental effect of excessive exposure to fluoride, usually in association with high natural levels of fluoride in the drinking water, is dental fluorosis11Public Health England. Water fluoridation. Health monitoring report for England 2018: Public Health England; 2018 [Available from: https://www.gov.uk/government/publications/water-fluoridation-health-monitoring-report-for-england-2018. Accessed April 24, 2020.. Other potential adverse side effects were examined, including increased prevalence of hip fracture, kidney stones, bladder cancer and osteosarcoma. The data did not associate water fluoridation with these potential complications11Public Health England. Water fluoridation. Health monitoring report for England 2018: Public Health England; 2018 [Available from: https://www.gov.uk/government/publications/water-fluoridation-health-monitoring-report-for-england-2018. Accessed April 24, 2020.. Other reviews have come to the same conclusion, i.e. that the major adverse effect of higher than recommended exposure to fluoride is dental fluorosis, it occurs in a dose-dependent fashion, and when mild to moderate is generally not an esthetic concern12McDonagh MS, Whiting PF, Wilson PM, Sutton AJ, Chestnutt I, Cooper J, et al. Systematic review of water fluoridation. BMJ. 2000;321(7265):855-9..
- The controversy over the association of water fluoridation/total fluoride exposure to cognitive development was again brought to the fore by the publication by Green et al in JAMA Pediatrics2Green R, Lanphear B, Hornung R, Flora D, Martinez-Mier EA, Neufeld R, et al. Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada. JAMA Pediatr. 2019.. Concurrently, the preliminary report of the association of fluoride intake within cognitive neurodevelopment by the NTP5NTP. 2019. Draft NTP Monograph on the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. Office of Health Assessment and Translation, Division of hte NTP, National Institute of Environmental Health Services, National Institutes of Health, US Department of Health and Human Services. was reviewed by an ad hoc committee of NAS6Review of the Draft NTP Monograph: Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. The National Academies Collection: Reports funded by National Institutes of Health. Washington (DC)2020., which questioned the preliminary findings of the NTP report that associated fluoride intake with lower IQ scores. This body of literature is challenging to summarize since many of the published studies are methodologically deficient6Review of the Draft NTP Monograph: Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. The National Academies Collection: Reports funded by National Institutes of Health. Washington (DC)2020.. For example, studies failed to consider all confounders that could influence the outcome variable, e.g. IQ. Quite surprisingly, the NTP review failed to include the large and comprehensive study from Sweden9Aggeborn L and Ohman M. Institute for Evaluation of Labour, Market and Education Policy (Sweden). Working Paper 2017: 20., which found no association between ingestion of fluoridated water and IQ. That study, as well as the Broadbent et. al study from New Zealand8Broadbent JM, Thomson WM, Ramrakha S, Moffitt TE, Zeng J, Foster Page LA, et al. Community Water Fluoridation and Intelligence: Prospective Study in New Zealand. Am J Public Health. 2015;105(1):72-6. are examples of research reports that meets the highest standards of scientific validity. Furthermore, with widespread use of topical fluoride in toothpaste, varnish and other modes of delivery, any evaluation of the effect of water fluoridation must consider these other sources of exposure.
- In response primarily to the findings that associate increased fluoride ingestion to dental fluorosis, the recommended concentration of fluoride in the drinking water was reduced to 0.7 ppm. As with all drugs and compounds that are used to prevent or treat human diseases, the minimum effective concentration, which is not associated with adverse events, is what is recommended. For water fluoridation, in the U.S. that is now 0.7 parts per million13U.S. Department of Health and Human Services Federal Panel on Community Water Fluoridation. U.S. Public Health Service Recommendation for Fluoride Concentration in Drinking Water for the Prevention of Dental Caries. Public Health Rep. 2015;130(4):318-31..
The question of the risk to benefit ratio of water fluoridation has been debated almost since the time that fluoridation was introduced into the water supply. The anti-fluoridationist arguments are often emotive and political, and do not always rely on the most scientifically sound data. Furthermore, interested members of the lay public are likely to derive their information from online sources, so dental professionals must be knowledgeable about the most current and scientifically valid information. A recent evaluation of the quality of information about water fluoridation available online determined that it was superficial, and sources of the information were not provided. Credibility was also a problem, particularly for websites that were classified as opposed to water fluoridation14Frangos Z, Steffens M, Leask J. Water fluoridation and the quality of information available online. Int Dent J. 2018;68(4):253-61.. As the discussion continues, debate must be based on sound scientific information, while limiting extraneous arguments. The benefits of water fluoridation have improved the quality of life of children and adults, with reduced prevalence of dental caries in the primary and permanent detentions, reduced need for restorative procedures and a marked reduction in painful dental abscesses early in life. Over the life course, this means improved oral health and reduced loss of teeth and edentulism. Further, in developing countries, where the introduction of fermentable carbohydrates in the diet has led to a jump in the caries rate, but routine dental services are not available, the use of water fluoridation represents a valuable approach to controlling dental disease15Whelton HP, Spencer AJ, Do LG, Rugg-Gunn AJ. Fluoride Revolution and Dental Caries: Evolution of Policies for Global Use. J Dent Res. 2019;98(8):837-46..
In summation, the importance of water fluoridation as a public health approach to reduce the caries rate is an established fact. Despite the evidence supporting the safety of water fluoridation at the appropriate concentration, this question will no doubt continue to be debated. As for all such discussions, the strength of the scientific evidence, with consideration of study methodology, must ultimately be the basis for policy decisions.
Table 1: IQ scores during childhood and adulthood when divided by exposure to fluoride8Broadbent JM, Thomson WM, Ramrakha S, Moffitt TE, Zeng J, Foster Page LA, et al. Community Water Fluoridation and Intelligence: Prospective Study in New Zealand. Am J Public Health. 2015;105(1):72-6.
|Fluoride exposure||IQ for children
|IQ for adults
1. Standardized population mean = 100.0
2. NS = no difference
3. These data are unadjusted. Similar outcomes are seen when the data are adjusted
- 1.Dominy SS, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333 https://www.ncbi.nlm.nih.gov/pubmed/30746447.
- 2.Sadrameli M, et al. Linking mechanisms of periodontitis to Alzheimer’s disease. Curr Opin Neurol. 2020;33(2):230-8 https://www.ncbi.nlm.nih.gov/pubmed/32097126.
- 3.Borsa L, et al. Analysis the link between periodontal diseases and Alzheimer’s disease: A systematic review. Int J Environ Res Public Health. 2021;18(17) https://www.ncbi.nlm.nih.gov/pubmed/34501899.
- 4.Costa MJF, et al. Relationship of Porphyromonas gingivalis and Alzheimer’s disease: A systematic review of pre-clinical studies. Clin Oral Investig. 2021;25(3):797-806 https://www.ncbi.nlm.nih.gov/pubmed/33469718.
- 5.Munoz Fernandez SS, Lima Ribeiro SM. Nutrition and Alzheimer disease. Clin Geriatr Med. 2018;34(4):677-97 https://www.ncbi.nlm.nih.gov/pubmed/30336995.
- 6.Aquilani R, et al. Is the Brain Undernourished in Alzheimer’s Disease? Nutrients. 2022;14(9) https://www.ncbi.nlm.nih.gov/pubmed/35565839.
- 7.Fukushima-Nakayama Y, et al. Reduced mastication impairs memory function. J Dent Res. 2017;96(9):1058-66 https://www.ncbi.nlm.nih.gov/pubmed/28621563.
- 8.Kim HB, et al. Abeta accumulation in vmo contributes to masticatory dysfunction in 5XFAD Mice. J Dent Res. 2021;100(9):960-7 https://www.ncbi.nlm.nih.gov/pubmed/33719684.
- 9.Miura H, et al. Relationship between cognitive function and mastication in elderly females. J Oral Rehabil. 2003;30(8):808-11 https://www.ncbi.nlm.nih.gov/pubmed/12880404.
- 10.Lexomboon D, et al. Chewing ability and tooth loss: association with cognitive impairment in an elderly population study. J Am Geriatr Soc. 2012;60(10):1951-6 https://www.ncbi.nlm.nih.gov/pubmed/23035667.
- 11.Elsig F, et al. Tooth loss, chewing efficiency and cognitive impairment in geriatric patients. Gerodontology. 2015;32(2):149-56 https://www.ncbi.nlm.nih.gov/pubmed/24128078.
- 12.Kim EK, et al. Relationship between chewing ability and cognitive impairment in the rural elderly. Arch Gerontol Geriatr. 2017;70:209-13 https://www.ncbi.nlm.nih.gov/pubmed/28214402.
- 13.Kim MS, et al. The association between mastication and mild cognitive impairment in Korean adults. Medicine (Baltimore). 2020;99(23):e20653 https://www.ncbi.nlm.nih.gov/pubmed/32502052.
- 14.Cardoso MG, et al. Relationship between functional masticatory units and cognitive impairment in elderly persons. J Oral Rehabil. 2019;46(5):417-23 https://www.ncbi.nlm.nih.gov/pubmed/30614023.
- 15.Popovac A, et al. Oral health status and nutritional habits as predictors for developing alzheimer’s disease. Med Princ Pract. 2021;30(5):448-54 https://www.ncbi.nlm.nih.gov/pubmed/34348313.
- 16.Park T, et al. More teeth and posterior balanced occlusion are a key determinant for cognitive function in the elderly. Int J Environ Res Public Health. 2021;18(4) https://www.ncbi.nlm.nih.gov/pubmed/33669490.
- 17.Lin CS, et al. Association between tooth loss and gray matter volume in cognitive impairment. Brain Imaging Behav. 2020;14(2):396-407 https://www.ncbi.nlm.nih.gov/pubmed/32170642.
- 18.Kumar S, et al. Oral health status and treatment need in geriatric patients with different degrees of cognitive impairment and dementia: a cross-sectional study. J Family Med Prim Care. 2021;10(6):2171-6 https://www.ncbi.nlm.nih.gov/pubmed/34322409.
- 19.Delwel S, et al. Chewing efficiency, global cognitive functioning, and dentition: A cross-sectional observational study in older people with mild cognitive impairment or mild to moderate dementia. Front Aging Neurosci. 2020;12:225 https://www.ncbi.nlm.nih.gov/pubmed/33033478.
- 20.Da Silva JD, et al. Association between cognitive health and masticatory conditions: a descriptive study of the national database of the universal healthcare system in Japan. Aging (Albany NY). 2021;13(6):7943-52 https://www.ncbi.nlm.nih.gov/pubmed/33739304.
- 21.Galindo-Moreno P, et al. The impact of tooth loss on cognitive function. Clin Oral Investig. 2022;26(4):3493-500 https://www.ncbi.nlm.nih.gov/pubmed/34881401.
- 22.Stewart R, et al. Adverse oral health and cognitive decline: The health, aging and body composition study. J Am Geriatr Soc. 2013;61(2):177-84 https://www.ncbi.nlm.nih.gov/pubmed/23405916.
- 23.Dintica CS, et al. The relation of poor mastication with cognition and dementia risk: A population-based longitudinal study. Aging (Albany NY). 2020;12(9):8536-48 https://www.ncbi.nlm.nih.gov/pubmed/32353829.
- 24.Kim MS, Han DH. Does reduced chewing ability efficiency influence cognitive function? Results of a 10-year national cohort study. Medicine (Baltimore). 2022;101(25):e29270 https://www.ncbi.nlm.nih.gov/pubmed/35758356.
- 25.Ko KA, et al. The Impact of Masticatory Function on Cognitive Impairment in Older Patients: A Population-Based Matched Case-Control Study. Yonsei Med J. 2022;63(8):783-9 https://www.ncbi.nlm.nih.gov/pubmed/35914761.
- 26.Garre-Olmo J. [Epidemiology of Alzheimer’s disease and other dementias]. Rev Neurol. 2018;66(11):377-86 https://www.ncbi.nlm.nih.gov/pubmed/29790571.
- 27.Stephan BCM, et al. Secular Trends in Dementia Prevalence and Incidence Worldwide: A Systematic Review. J Alzheimers Dis. 2018;66(2):653-80 https://www.ncbi.nlm.nih.gov/pubmed/30347617.
- 28.Lopez OL, Kuller LH. Epidemiology of aging and associated cognitive disorders: Prevalence and incidence of Alzheimer’s disease and other dementias. Handb Clin Neurol. 2019;167:139-48 https://www.ncbi.nlm.nih.gov/pubmed/31753130.
- 29.Ono Y, et al. Occlusion and brain function: mastication as a prevention of cognitive dysfunction. J Oral Rehabil. 2010;37(8):624-40 https://www.ncbi.nlm.nih.gov/pubmed/20236235.
- 30.Kubo KY, et al. Masticatory function and cognitive function. Okajimas Folia Anat Jpn. 2010;87(3):135-40 https://www.ncbi.nlm.nih.gov/pubmed/21174943.
- 31.Chen H, et al. Chewing Maintains Hippocampus-Dependent Cognitive Function. Int J Med Sci. 2015;12(6):502-9 https://www.ncbi.nlm.nih.gov/pubmed/26078711.
- 32.Azuma K, et al. Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review. Int J Mol Sci. 2017;18(8) https://www.ncbi.nlm.nih.gov/pubmed/28771175.
- 33.Chuhuaicura P, et al. Mastication as a protective factor of the cognitive decline in adults: A qualitative systematic review. Int Dent J. 2019;69(5):334-40 https://www.ncbi.nlm.nih.gov/pubmed/31140598.
- 34.Lopez-Chaichio L, et al. Oral health and healthy chewing for healthy cognitive ageing: A comprehensive narrative review. Gerodontology. 2021;38(2):126-35 https://www.ncbi.nlm.nih.gov/pubmed/33179281.
- 35.Tada A, Miura H. Association between mastication and cognitive status: A systematic review. Arch Gerontol Geriatr. 2017;70:44-53 https://www.ncbi.nlm.nih.gov/pubmed/28042986.
- 36.Ahmed SE, et al. Influence of Dental Prostheses on Cognitive Functioning in Elderly Population: A Systematic Review. J Pharm Bioallied Sci. 2021;13(Suppl 1):S788-S94 https://www.ncbi.nlm.nih.gov/pubmed/34447202.
- 37.Tonsekar PP, et al. Periodontal disease, tooth loss and dementia: Is there a link? A systematic review. Gerodontology. 2017;34(2):151-63 https://www.ncbi.nlm.nih.gov/pubmed/28168759.
- 38.Nangle MR, Manchery N. Can chronic oral inflammation and masticatory dysfunction contribute to cognitive impairment? Curr Opin Psychiatry. 2020;33(2):156-62 https://www.ncbi.nlm.nih.gov/pubmed/31895157.
- 39.Nakamura T, et al. Oral dysfunctions and cognitive impairment/dementia. J Neurosci Res. 2021;99(2):518-28 https://www.ncbi.nlm.nih.gov/pubmed/33164225.
- 40.Weijenberg RAF, et al. Mind your teeth-The relationship between mastication and cognition. Gerodontology. 2019;36(1):2-7 https://www.ncbi.nlm.nih.gov/pubmed/30480331.
- 41.Asher S, et al. Periodontal health, cognitive decline, and dementia: A systematic review and meta-analysis of longitudinal studies. J Am Geriatr Soc. 2022;70(9):2695-709 https://www.ncbi.nlm.nih.gov/pubmed/36073186.
- 42.Lin CS. Revisiting the link between cognitive decline and masticatory dysfunction. BMC Geriatr. 2018;18(1):5 https://www.ncbi.nlm.nih.gov/pubmed/29304748.
- 43.Wu YT, et al. The changing prevalence and incidence of dementia over time – current evidence. Nat Rev Neurol. 2017;13(6):327-39 https://www.ncbi.nlm.nih.gov/pubmed/28497805.
- 44.National Psoriasis Foundation. Soriatane (Acitretin). https://www.psoriasis.org/soriatane-acitretin/.
- 45.National Psoriasis Foundation. Current Biologics on the Market. https://www.psoriasis.org/current-biologics-on-the-market/.
- 46.Dalmády S, Kemény L, Antal M, Gyulai R. Periodontitis: a newly identified comorbidity in psoriasis and psoriatic arthritis. Expert Rev Clin Immunol 2020;16(1):101-8. doi: 10.1080/1744666X.2019.1700113.