Review Article| Volume 22, ISSUE 10, P2039-2045, October 2021

Dose-Response Meta-Analysis on Tooth Loss With the Risk of Cognitive Impairment and Dementia



      To quantify the dose-response associations between tooth loss and risk of cognitive impairment and dementia.


      Longitudinal studies that examined the association between tooth loss and cognitive function were systematically searched on 6 databases through March 1, 2020. The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Risk estimates were pooled using random-effects models. The dose-response associations were assessed using generalized least squares spline models.

      Setting and Participants

      Adults from community, institution, outpatient or in-hospital were included in the meta-analysis.


      Cognitive impairment and dementia were defined by neuropsychological tests, diagnostic criteria, or medical records. Tooth loss was self-reported or assessed by clinical examinations.


      Fourteen studies were entered into the meta-analysis, including 34,074 participants and 4689 cases with diminished cognitive function. Participants with more tooth loss had a 1.48 times higher risk of developing cognitive impairment [95% confidence interval (CI) 1.18–1.87] and 1.28 times higher risk of being diagnosed with dementia (95% CI 1.09–1.49); however, the association was nonsignificant for participants using dentures (relative risk = 1.10, 95% CI 0.90–1.11). Eight studies were included in the dose-response analysis, and data supported the use of linear models. Each additional tooth loss was associated with a 0.014 increased relative risk of cognitive impairment and 0.011 elevated relative risks of dementia. Edentulous participants faced a 1.54 times higher risk of cognitive impairment and a 1.40 times higher risk of being diagnosed with dementia.

      Conclusions and Implications

      Moderate-quality evidence suggested tooth loss was independently associated with cognitive impairment and dementia; risk of diminished cognitive function increased with incremental numbers of teeth lost. Furthermore, timely prosthodontic treatment with dentures may reduce the progression of cognitive decline related to tooth loss.


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        • Nichols E.
        • Vos T.
        Estimating the global mortality from Alzheimer’s disease and other dementias: A new method and results from the Global Burden of Disease study 2019: Epidemiology/prevalence, incidence, and outcomes of MCI and dementia.
        Alzheimers Dement. 2020; 16: e042236
        • Matthews K.A.
        • Xu W.
        • Gaglioti A.H.
        • et al.
        Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥65 years.
        Alzheimers Dement. 2019; 15: 17-24
        • Gatz M.
        • Mortimer J.A.
        • Fratiglioni L.
        • et al.
        Potentially modifiable risk factors for dementia in identical twins.
        Alzheimers Dement. 2006; 2: 110-117
        • Petersen R.C.
        • Morris J.C.
        Mild cognitive impairment as a clinical entity and treatment target.
        Arch Neurol. 2005; 62: 1160
        • Werner P.
        Mild cognitive impairment: Conceptual, assessment, ethical, and social issues.
        Clin Interv Aging. 2008; 3: 413-420
        • Griffin S.O.
        • Jones J.A.
        • Brunson D.
        • et al.
        Burden of oral disease among older adults and implications for public health priorities.
        Am J Public Health. 2012; 102: 411-418
        • Delwel S.
        • Binnekade T.T.
        • Perez R.S.G.M.
        • et al.
        Oral hygiene and oral health in older people with dementia: A comprehensive review with focus on oral soft tissues.
        Clin Oral Investig. 2018; 22: 93-108
        • Boyd M.
        • Broad J.B.
        • Kerse N.
        • et al.
        Twenty-year trends in dependency in residential aged care in Auckland, New Zealand: A descriptive study.
        J Am Med Dir Assoc. 2011; 12: 535-540
        • Cerutti-Kopplin D.
        • Feine J.
        • Padilha D.M.
        • et al.
        Tooth loss increases the risk of diminished cognitive function: A systematic review and meta-analysis.
        JDR Clin Transl Res. 2016; 1: 10-19
        • Daly B.
        • Thompsell A.
        • Sharpling J.
        • et al.
        Evidence summary: The relationship between oral health and dementia.
        Br Dent J. 2017; 223: 846-853
        • Fang W.
        • Jiang M.
        • Gu B.
        • et al.
        Tooth loss as a risk factor for dementia: Systematic review and meta-analysis of 21 observational studies.
        BMC Psychiatry. 2018; 18: 345
        • Oh B.
        • Han D.-H.
        • Han K.-T.
        • et al.
        Association between residual teeth number in later life and incidence of dementia: A systematic review and meta-analysis.
        BMC Geriatr. 2018; 18: 48
        • Shen T.
        • Lv J.
        • Wang L.
        • et al.
        Association between tooth loss and dementia among older people: A meta-analysis: Association between tooth loss and dementia among older people.
        Int J Geriatr Psychiatry. 2016; 31: 953-955
        • Tonsekar P.P.
        • Jiang S.S.
        • Yue G.
        Periodontal disease, tooth loss and dementia: Is there a link? A systematic review.
        Gerodontology. 2017; 34: 151-163
        • Wu B.
        • Fillenbaum G.G.
        • Plassman B.L.
        • Guo L.
        Association between oral health and cognitive status: A systematic review.
        J Am Geriatr Soc. 2016; 64: 739-751
        • Chen J.
        • Ren C.-J.
        • Wu L.
        • et al.
        Tooth loss is associated with increased risk of dementia and with a dose-response relationship.
        Front Aging Neurosci. 2018; 10: 415
        • Dintica C.S.
        • Rizzuto D.
        • Marseglia A.
        • et al.
        Tooth loss is associated with accelerated cognitive decline and volumetric brain differences: A population-based study.
        Neurobiol Aging. 2018; 67: 23-30
        • Hatta K.
        • Ikebe K.
        • Gondo Y.
        • et al.
        Influence of lack of posterior occlusal support on cognitive decline among 80-year-old Japanese people in a 3-year prospective study: Influence of occlusion on cognition.
        Geriatr Gerontol Int. 2018; 18: 1439-1446
        • Saito S.
        • Ohi T.
        • Murakami T.
        • et al.
        Association between tooth loss and cognitive impairment in community-dwelling older Japanese adults: A 4-year prospective cohort study from the Ohasama study.
        BMC Oral Health. 2018; 18: 142
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • The PRISMA Group
        Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement.
        PLoS Med. 2009; 6: e1000097
        • Stang A.
        Critical evaluation of the Newcastle-Ottawa Scale for the assessment of the quality of non-randomized studies in meta-analyses.
        Eur J Epidemiol. 2010; 25: 603-605
        • Guyatt G.H.
        • Oxman A.D.
        • Vist G.E.
        • et al.
        GRADE: An emerging consensus on rating quality of evidence and strength of recommendations.
        BMJ. 2008; 336: 924-926
        • Higgins J.P.T.
        • Thomas J.
        • Chandler J.
        • et al.
        Cochrane Handbook for Systematic Reviews of Interventions. 2nd. John Wiley & Sons, Chichester (UK)2019
        • Greenland S.
        • Longnecker M.P.
        Methods for trend estimation from summarized dose-response data, with applications to meta-analysis.
        Am J Epidemiol. 1992; 135: 1301-1309
        • Harre F.E.
        • Lee K.L.
        • Pollock B.G.
        Regression models in clinical studies: Determining relationships between predictors and response.
        J Natl Cancer Inst. 1988; 80: 1198-1202
        • Arrivé E.
        • Letenneur L.
        • Matharan F.
        • et al.
        Oral health condition of French elderly and risk of dementia: A longitudinal cohort study: Elderly’s oral health and risk of dementia.
        Community Dent Oral Epidemiol. 2012; 40: 230-238
        • Batty G.-D.
        • Li Q.
        • Huxley R.
        • et al.
        Oral disease in relation to future risk of dementia and cognitive decline: Prospective cohort study based on the action in diabetes and vascular disease: Preterax and Diamicron Modified-Release Controlled Evaluation (Advance) Trial.
        Eur Psychiatry. 2013; 28: 49-52
        • Paganini-Hill A.
        • White S.C.
        • Atchison K.A.
        Dentition, dental health habits, and dementia: The Leisure World Cohort Study.
        J Am Geriatr Soc. 2012; 60: 1556-1563
        • Okamoto N.
        • Morikawa M.
        • Tomioka K.
        • et al.
        Association between tooth loss and the development of mild memory impairment in the elderly: The Fujiwara-kyo Study.
        J Alzheimers Dis. 2015; 44: 777-786
        • Shimazaki Y.
        • Soh I.
        • Saito T.
        • et al.
        Influence of dentition status on physical disability, mental impairment, and mortality in institutionalized elderly people.
        J Dent Res. 2001; 80: 340-345
        • Stein P.S.
        • Desrosiers M.
        • Donegan S.J.
        • et al.
        Tooth loss, dementia and neuropathology in the Nun Study.
        J Am Dent Assoc. 2007; 138: 1314-1322
        • Stewart R.
        • Stenman U.
        • Hakeberg M.
        • et al.
        Associations between oral health and risk of dementia in a 37-year follow-up study: The prospective population study of women in Gothenburg.
        J Am Geriatr Soc. 2015; 63: 100-105
        • Takeuchi K.
        • Ohara T.
        • Furuta M.
        • et al.
        Tooth loss and risk of dementia in the community: The Hisayama Study.
        J Am Geriatr Soc. 2017; 65: e95-e100
        • Yamamoto T.
        • Kondo K.
        • Hirai H.
        • et al.
        Association between self-reported dental health status and onset of dementia: A 4-year prospective cohort study of older Japanese adults from the Aichi Gerontological Evaluation Study (AGES) Project.
        Psychosom Med. 2012; 74: 241-248
        • Kim J.-M.
        • Stewart R.
        • Prince M.
        • et al.
        Dental health, nutritional status and recent-onset dementia in a Korean community population.
        Int J Geriatr Psychiatry. 2007; 22: 850-855
        • Yang H.-L.
        • Li F.-R.
        • Chen P.-L.
        • et al.
        Tooth loss, denture use, and cognitive impairment in Chinese older adults: A community cohort study.
        J Gerontol A Biol Sci Med Sci. 2021 Mar 1.; ([E-pub ahead of print])
        • Shin M.
        • Shin Y.J.
        • Karna S.
        • Kim H.
        Rehabilitation of lost teeth related to maintenance of cognitive function.
        Oral Dis. 2019; 25: 290-299
        • Cerutti-Kopplin D.
        • Emami E.
        • Hilgert J.B.
        • et al.
        Cognitive status of edentate elders wearing complete denture: Does quality of denture matter?.
        J Dent. 2015; 43: 1071-1075
        • Kubo K.
        • Ichihashi Y.
        • Kurata C.
        • et al.
        Masticatory function and cognitive function.
        Okajimas Folia Anat Jpn. 2010; 87: 135-140
        • Chen H.
        • Iinuma M.
        • Onozuka M.
        • Kubo K.-Y.
        Chewing maintains hippocampus-dependent cognitive function.
        Int J Med Sci. 2015; 12: 502-509
        • Utsugi C.
        • Miyazono S.
        • Osada K.
        • et al.
        Hard-diet feeding recovers neurogenesis in the subventricular zone and olfactory functions of mice impaired by soft-diet feeding.
        PLoS One. 2014; 9: e97309
        • Katayama T.
        • Mori D.
        • Miyake H.
        • et al.
        Effect of bite-raised condition on the hippocampal cholinergic system of aged SAMP8 mice.
        Neurosci Lett. 2012; 520: 77-81
        • Tang X.
        • Pan Y.
        • Zhao Y.
        Vitamin D inhibits the expression of interleukin-8 in human periodontal ligament cells stimulated with Porphyromonas gingivalis.
        Arch Oral Biol. 2013; 58: 397-407
        • Jayedi A.
        • Rashidy-Pour A.
        • Shab-Bidar S.
        Vitamin D status and risk of dementia and Alzheimer’s disease: A meta-analysis of dose-response.
        Nutr Neurosci. 2019; 22: 750-759
        • Singhrao S.K.
        • Olsen I.
        Are Porphyromonas gingivalis outer membrane vesicles microbullets for sporadic Alzheimer’s disease manifestation?.
        J Alzheimers Dis Rep. 2018; 2: 219-228
        • Nie R.
        • Wu Z.
        • Ni J.
        • et al.
        Porphyromonas gingivalis infection induces amyloid-β accumulation in monocytes/macrophages.
        J Alzheimers Dis. 2019; 72: 479-494
        • Dominy S.S.
        • Lynch C.
        • Ermini F.
        • et al.
        Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors.
        Sci Adv. 2019; 5: eaau3333
        • Kaye E.K.
        • Valencia A.
        • Baba N.
        • et al.
        Tooth loss and periodontal disease predict poor cognitive function in older men: Periodontal disease and cognitive function.
        J Am Geriatr Soc. 2010; 58: 713-718
        • Noble J.M.
        • Scarmeas N.
        • Celenti R.S.
        • et al.
        Serum IgG antibody levels to periodontal microbiota are associated with incident Alzheimer disease.
        PLoS One. 2014; 9: e114959
        • Abbayya K.
        • Chidambar Y.
        • Naduwinmani S.
        • Puthanakar N.
        Association between periodontitis and Alzheimer′s disease.
        North Am J Med Sci. 2015; 7: 241
        • Weijenberg R.A.F.
        • Delwel S.
        • Ho B.V.
        • et al.
        Mind your teeth—the relationship between mastication and cognition.
        Gerodontology. 2019; 36: 2-7
        • Rogers M.A.M.
        • Plassman B.L.
        • Kabeto M.
        • et al.
        Parental education and late-life dementia in the United States.
        J Geriatr Psychiatry Neurol. 2009; 22: 71-80
        • Thomson W.M.
        • Barak Y.
        Tooth loss and dementia: A critical examination.
        J Dent Res. 2021; 100: 226-231
        • Naorungroj S.
        • Slade G.D.
        • Beck J.D.
        • et al.
        Cognitive decline and oral health in middle-aged adults in the ARIC study.
        J Dent Res. 2013; 92: 795-801
        • Kang J.
        • Wu B.
        • Bunce D.
        • et al.
        Cognitive function and oral health among ageing adults.
        Community Dent Oral Epidemiol. 2019; 47: 259-266
        • Caruana E.J.
        • Roman M.
        • Hernández-Sánchez J.
        • Solli P.
        Longitudinal studies.
        J Thorac Dis. 2015; 7: E537-E540
        • Hartling L.
        • Milne A.
        • Hamm M.P.
        • et al.
        Testing the Newcastle Ottawa Scale showed low reliability between individual reviewers.
        J Clin Epidemiol. 2013; 66: 982-993