Actual problems in dentistry Actual problems in dentistry Проблемы стоматологии 2077-7566 2412-9461 50839 10.18481/2077-7566-2022-18-2-173-180 ДИАГНОСТИКА СТОМАТОЛОГИЧЕСКИХ ЗАБОЛЕВАНИЙ DIAGNOSIS OF DENTAL DISEASES ДИАГНОСТИКА СТОМАТОЛОГИЧЕСКИХ ЗАБОЛЕВАНИЙ ASSESSMENT OF THE CONDITION OF THE ORAL CAVITY IN EARLY DIAGNOSIS OF COGNITIVE DEFICITS ОЦЕНКА СОСТОЯНИЯ ПОЛОСТИ РТА В РАННЕЙ ДИАГНОСТИКЕ КОГНИТИВНОГО ДЕФИЦИТА Мякотных Виктор Степанович Myakotnykh Viktor Stepanovich vmaykotnykh@yandex.ru

доктор медицинских наук;

doctor of medical sciences;

 Харитонова Марина Павловна Kharitonova Marina P. nocar@sosp.ru

доктор медицинских наук;

doctor of medical sciences;

 Сиденкова Алена Петровна Silenkova Alena Petrovna sidenkovs@mail.ru

доктор медицинских наук;

doctor of medical sciences;

 Мещанинов Виктор Николаевич Meshchaninov Viktor Nikolaevich mv-02@yandex.ru

доктор медицинских наук;

doctor of medical sciences;

 Уральский государственный медицинский университет Екатеринбург Россия Ural State Medical University Yekaterinburg Russian Federation Уральский государственный медицинский университет Ural State Medical University Уральский государственный медицинский университет Екатеринбург Россия Уральский государственный медицинский университет Yekaterinburg Russian Federation Уральский государственный медицинский университет Екатеринбург Россия Ural State Medical University Yekaterinburg Russian Federation 18 08 2022 18 08 2022 18 2 173 180 08 06 2022 https://dental-press.ru/en/nauka/article/50839/view

Предметом исследования явилось сопоставление всесторонней оценки состояния ротовой полости с присутствием или вероятностью формирования когнитивного дефицита — на основании данных литературы и результатов собственных наблюдений. Цель исследования — проведение сравнительного анализа нетравматической потери зубов у лиц разного возраста без признаков когнитивного дефицита и в возрасте 60 лет и старше с признаками деменции, и на этом основании — определение возможности использования данных о состоянии зубного ряда в качестве «точки отсчета» для дальнейшего прогнозирования когнитивного снижения. На первом этапе исследования проведено изучение возрастной динамики состояния зубов у 110 пациентов в возрасте 24–89 лет, на втором этапе — подсчет количества отсутствующих зубов у 93 пациентов психогериатрического стационара в возрасте 60 лет и старше, страдающих деменцией. Обсуждение полученных результатов при их сравнении с литературными данными показало, что отсутствие значительного количества зубов у лиц старшего возраста в результате нетравматической потери может служить «точкой отсчета» для проведения дальнейшего углубленного, комплексного обследования буккального эпителия, ротовой жидкости как суррогатных тканей, состояние которых способно указывать на патологию головного мозга. Представлен возможный алгоритм такого рода исследования, включающий несколько этапов: общую оценку состояния полости рта с акцентом на выраженную потерю зубов нетравматического генеза в возрасте 50 лет и старше; исследование ротовой полости на присутствие патологического микробного обсеменения; определение состояния ядер буккальной цитограммы и уровней содержания белка S100В, Aβ и тау-белка в ротовой жидкости. Данный алгоритм может оказаться удобным и легковыполнимым скрининг-методом ранней диагностики когнитивного дефицита.

The subject of the study was a comparison of a comprehensive assessment of the state of the oral cavity with the presence or probability of the formation of cognitive deficits – based on literature data and the results of their own observations. The aim of the study is to conduct a comparative analysis of non-traumatic tooth loss in people of different ages without signs of cognitive deficit and at the age of 60 years and older with signs of dementia and, on this basis, to determine the possibility of using data on the state of the dentition as a "reference point" for further predicting cognitive decline. At the 1st stage of the study, the age dynamics of the dental condition was studied in 110 patients aged 24–89 years, at the 2nd stage – counting the number of missing teeth in 93 patients of a psychogeriatric hospital aged 60 years and older suffering from dementia. The discussion of the results obtained when compared with the literature data showed that the absence of a significant number of teeth in older people as a result of their non-traumatic loss can serve as a "reference point" for further in-depth, comprehensive examination of the buccal epithelium, oral fluid as surrogate tissues, the condition of which may indicate brain pathology. A possible algorithm of this kind of research is presented, including several stages: a general assessment of the condition of the oral cavity with an emphasis on pronounced tooth loss of non-traumatic genesis at the age of 50 years and older; examination of the oral cavity for the presence of pathological microbial contamination; determination of the state of buccal cytogram nuclei and levels of protein S100B, Aβ and tau protein in the oral fluid. This algorithm may prove to be a convenient and easily feasible screening method for early diagnosis of cognitive deficits.

 ротовая полость зубы нейродегенеративный процесс когнитивные расстройства алгоритм исследования состояния полости рта oral cavity teeth neurodegenerative process cognitive disorders algorithm for the study of the state of the oral cavity

Мякотных В.С., Мещанинов В.Н., Боровкова Т.А., Сиденкова А.П. Теория и практика современной геронтологии. Екатеринбург : ООО «ИИЦ «Знак качества». 2022:280. [V.S. Myakotnykh, V.N. Meshchaninov, T.A. Borovkova, A.P. Sidenkova. Theory and practice of modern gerontology. Yekaterinburg : LLC "IIC "Quality mark". 2022:280. (In Russ.)]. https://www.twirpx.com/file/3712018/ Myakotnyh V.S., Meschaninov V.N., Borovkova T.A., Sidenkova A.P. Teoriya i praktika sovremennoy gerontologii. Ekaterinburg : OOO «IIC «Znak kachestva». 2022:280. [V.S. Myakotnykh, V.N. Meshchaninov, T.A. Borovkova, A.P. Sidenkova. Theory and practice of modern gerontology. Yekaterinburg : LLC "IIC "Quality mark". 2022:280. (In Russ.)]. https://www.twirpx.com/file/3712018/ Cao Q., Tan C-C., Xu W., Hu H., Cao X., Dong Q., Tan L., Yu J.-T. The prevalence of dementia: A systematic review and meta-analysi // J. Alzheimer's Disease. - 2020;73(3):1157-1166. http://doi.org/10.3233/JAD-191092 Cao Q., Tan C-C., Xu W., Hu H., Cao X., Dong Q., Tan L., Yu J.-T. The prevalence of dementia: A systematic review and meta-analysi // J. Alzheimer's Disease. - 2020;73(3):1157-1166. http://doi.org/10.3233/JAD-191092 Reinhardt M.M., Cohen C.I. Late-life psychosis: Diagnosis and treatment // Curr. Psychiatry Rep. - 2015;17(2):1-13. http://doi.org/10.1007/s11920-014-0542-0 Reinhardt M.M., Cohen C.I. Late-life psychosis: Diagnosis and treatment // Curr. Psychiatry Rep. - 2015;17(2):1-13. http://doi.org/10.1007/s11920-014-0542-0 Базарный В.В., Сиденкова А.П., Резайкин А.В., Мякотных В.С., Боровкова Т.А., Селькина Е.О., Полушина Л.Г., Максимова А.Ю., Ванькова Е.А. Возможность использования результатов исследования ротовой жидкости и буккального эпителия в диагностике болезни Альцгеймера. Успехи геронтол. 2021;34(4):550-557. [V.V. Bazarny, A.P. Sidenkova, A.V. Rezaykin, V.S. Myakotnykh, T.A. Borovkova, E.O. Selkina, L. G. Polushina, A. Yu. Maksimova, E. A. Vankova. The possibility of using the results of the study of oral fluid and buccal epithelium in the diagnosis of Alzheimer's disease. Adv. Gerontol. 2021;34(4):550-557. (In Russ.)]. http://doi.org/10.34922/AE.2021.34.4.007 Bazarnyy V.V., Sidenkova A.P., Rezaykin A.V., Myakotnyh V.S., Borovkova T.A., Sel'kina E.O., Polushina L.G., Maksimova A.Yu., Van'kova E.A. Vozmozhnost' ispol'zovaniya rezul'tatov issledovaniya rotovoy zhidkosti i bukkal'nogo epiteliya v diagnostike bolezni Al'cgeymera. Uspehi gerontol. 2021;34(4):550-557. [V.V. Bazarny, A.P. Sidenkova, A.V. Rezaykin, V.S. Myakotnykh, T.A. Borovkova, E.O. Selkina, L. G. Polushina, A. Yu. Maksimova, E. A. Vankova. The possibility of using the results of the study of oral fluid and buccal epithelium in the diagnosis of Alzheimer's disease. Adv. Gerontol. 2021;34(4):550-557. (In Russ.)]. http://doi.org/10.34922/AE.2021.34.4.007 Зуев В.А., Дятлова А.С., Линькова Н.С., Кветная Т.В. Экспрессия аb42, t-протеина, р16, р53 в буккальном эпителии: перспективы диагностики болезни Альцгеймера и темпа старения организма. Бюл. экспер. биол. 2018;11:627-631. [V.A. Zuev, A.S. Dyatlova, N.S. Linkova, T.V. Kvetnaya. Expression of ab42, t-protein, p16, p53 in buccal epithelium: prospects for the diagnosis of Alzheimer's disease and the rate of aging of the body. Byul. exper. biol. 2018;11:627-631. (In Russ.)]. https://www.elibrary.ru/item.asp?id = 36380508 Zuev V.A., Dyatlova A.S., Lin'kova N.S., Kvetnaya T.V. Ekspressiya ab42, t-proteina, r16, r53 v bukkal'nom epitelii: perspektivy diagnostiki bolezni Al'cgeymera i tempa stareniya organizma. Byul. eksper. biol. 2018;11:627-631. [V.A. Zuev, A.S. Dyatlova, N.S. Linkova, T.V. Kvetnaya. Expression of ab42, t-protein, p16, p53 in buccal epithelium: prospects for the diagnosis of Alzheimer's disease and the rate of aging of the body. Byul. exper. biol. 2018;11:627-631. (In Russ.)]. https://www.elibrary.ru/item.asp?id = 36380508 Lee M., Guo J.-P., Kennedy K., McGeer E.G., McGeer P.L. A Method for Diagnosing Alzheimer’s Disease Based on Salivary Amyloid-β Protein 42 Levels // J. Alzheimer's Dis. - 2017;55(3):1175-1182. https://doi.org/10.3233/JAD-160748 Lee M., Guo J.-P., Kennedy K., McGeer E.G., McGeer P.L. A Method for Diagnosing Alzheimer’s Disease Based on Salivary Amyloid-β Protein 42 Levels // J. Alzheimer's Dis. - 2017;55(3):1175-1182. https://doi.org/10.3233/JAD-160748 Yilmaz A., Geddes T., Han B., Bahado-Singh R.O., Wilson G.D., Imam K., Maddens M., Graham S.F. Diagnostic Biomarkers of Alzheimer’s Disease as Identified in Saliva using 1H NMR-Based Metabolomics // J. Alzheimer's Dis. - 2017;58(2):355-359. https://doi.org/10.3233/JAD-161226 Yilmaz A., Geddes T., Han B., Bahado-Singh R.O., Wilson G.D., Imam K., Maddens M., Graham S.F. Diagnostic Biomarkers of Alzheimer’s Disease as Identified in Saliva using 1H NMR-Based Metabolomics // J. Alzheimer's Dis. - 2017;58(2):355-359. https://doi.org/10.3233/JAD-161226 Пальцев М.А., Кветной И.М., Полякова В.О., Литвякова О.М., Севастьянова Н.Н., Дурнова А.О., Толибова Г.Х. Сигнальные молекулы в буккальном эпителии: оптимизация диагностики социально значимых заболеваний. Молекулярная медицина. 2012;4:18-23. [M.A. Palcev, I.M. Kvetnoy, V.O. Polyakova, O.M Litvyakova., N.N. Sevastyanova, A.O. Durnova, G.H. Tolibova. Signaling molecules in buccal epithelium: optimization of diagnostics of socially significant diseases. Molecular Medicine. 2012;4:18-23. (In Russ.)]. https://cyberleninka.ru/article/n/signalnye-molekuly-v-bukkalnom-epitelii-optimizatsiya-diagnostiki-sotsialno-znachimyh-zabolevaniy Pal'cev M.A., Kvetnoy I.M., Polyakova V.O., Litvyakova O.M., Sevast'yanova N.N., Durnova A.O., Tolibova G.H. Signal'nye molekuly v bukkal'nom epitelii: optimizaciya diagnostiki social'no znachimyh zabolevaniy. Molekulyarnaya medicina. 2012;4:18-23. [M.A. Palcev, I.M. Kvetnoy, V.O. Polyakova, O.M Litvyakova., N.N. Sevastyanova, A.O. Durnova, G.H. Tolibova. Signaling molecules in buccal epithelium: optimization of diagnostics of socially significant diseases. Molecular Medicine. 2012;4:18-23. (In Russ.)]. https://cyberleninka.ru/article/n/signalnye-molekuly-v-bukkalnom-epitelii-optimizatsiya-diagnostiki-sotsialno-znachimyh-zabolevaniy Hattori H., Matsumoto M., Iwai K., Tsuchiya H., Miyauchi E., Takasaki M., Kamino К., Munehira J., Kimura Y., Kawanishi K., Hoshino T., Murai H., Ogata H., Maruyama H., Yoshida H. The tau protein of oral epithelium increases in Alzheimer's disease // J. Gerontol. A Biol. Sci. Med. Sci. - 2002;57(1):64-70. http://doi.org/10.1093/gerona/57.1.m64 Hattori H., Matsumoto M., Iwai K., Tsuchiya H., Miyauchi E., Takasaki M., Kamino K., Munehira J., Kimura Y., Kawanishi K., Hoshino T., Murai H., Ogata H., Maruyama H., Yoshida H. The tau protein of oral epithelium increases in Alzheimer's disease // J. Gerontol. A Biol. Sci. Med. Sci. - 2002;57(1):64-70. http://doi.org/10.1093/gerona/57.1.m64 François M., Leifert W., Martins R., Thomas P., Fenech M. Biomarkers of Alzheimer’s Disease Risk in Peripheral Tissues; Focus on Buccal Cells // Cur. Alzheimer Res. - 2014;11(6):519-531. http://doi.org/10.2174/1567205011666140618103827 François M., Leifert W., Martins R., Thomas P., Fenech M. Biomarkers of Alzheimer’s Disease Risk in Peripheral Tissues; Focus on Buccal Cells // Cur. Alzheimer Res. - 2014;11(6):519-531. http://doi.org/10.2174/1567205011666140618103827 Michetti F., D'Ambrosi N., Toesca A., Puglisi M.A., Serrano A., Marchese E., Corvino V., Geloso M.C. The S100B story: from biomarker to active factor in neural injury // J. Neurochem. - 2018;148(2):168-187. https://doi.org/10.1111/jnc.14574 Michetti F., D'Ambrosi N., Toesca A., Puglisi M.A., Serrano A., Marchese E., Corvino V., Geloso M.C. The S100B story: from biomarker to active factor in neural injury // J. Neurochem. - 2018;148(2):168-187. https://doi.org/10.1111/jnc.14574 Калашникова С.А., Полякова Л.В. Использование бактериального липополисахарида для моделирования патологических процессов в медико-биологических исследованиях (обзор литературы). Вестн. новых мед. технологий. 2017;24(2):209-219. [S.A. Kalashnikova, L.V. Polyakova. The use of bacterial lipopolysaccharide for modeling pathological processes in biomedical research (literature review). Herald new medical technologies. 2017;24(2):209-219. (In Russ.)]. http://doi.org/10.12737/article_5947d50a4ddf68.91843258 Kalashnikova S.A., Polyakova L.V. Ispol'zovanie bakterial'nogo lipopolisaharida dlya modelirovaniya patologicheskih processov v mediko-biologicheskih issledovaniyah (obzor literatury). Vestn. novyh med. tehnologiy. 2017;24(2):209-219. [S.A. Kalashnikova, L.V. Polyakova. The use of bacterial lipopolysaccharide for modeling pathological processes in biomedical research (literature review). Herald new medical technologies. 2017;24(2):209-219. (In Russ.)]. http://doi.org/10.12737/article_5947d50a4ddf68.91843258 Wingrove J.A., DiScipio R.G., Chen Z., Potempa J., Travis J., Hugli T.E. Activation of Complement Components C3 and C5 by a Cysteine Proteinase (Gingipain-1) from Porphyromonus (Bacteroides) gingivalis // J. Biol. Chem. - 1992;267(26):18902-18907. https://doi.org/10.1016/S0021-9258(19)37046-2 Wingrove J.A., DiScipio R.G., Chen Z., Potempa J., Travis J., Hugli T.E. Activation of Complement Components C3 and C5 by a Cysteine Proteinase (Gingipain-1) from Porphyromonus (Bacteroides) gingivalis // J. Biol. Chem. - 1992;267(26):18902-18907. https://doi.org/10.1016/S0021-9258(19)37046-2 Семенцова Е.А., Мандра Ю.В., Базарный В.В., Полушина Л.Г., Светлакова Е.Н. Маркеры возрастных изменений, определяемые в тканях полости рта (обзор литературы). Успехи геронтол. 2021;34(2):217-225. [E.A. Sementsova, Yu.V. Mandra, V.V. Bazarny, L.G. Polushina, E.N. Svetlakova. Markers of age-related changes determined in the tissues of the oral cavity (literature review). Adv. gerontol. 2021;34(2):217-225. (In Russ.)]. http://doi.org/10.34922/AE.2021.34.2.005 Semencova E.A., Mandra Yu.V., Bazarnyy V.V., Polushina L.G., Svetlakova E.N. Markery vozrastnyh izmeneniy, opredelyaemye v tkanyah polosti rta (obzor literatury). Uspehi gerontol. 2021;34(2):217-225. [E.A. Sementsova, Yu.V. Mandra, V.V. Bazarny, L.G. Polushina, E.N. Svetlakova. Markers of age-related changes determined in the tissues of the oral cavity (literature review). Adv. gerontol. 2021;34(2):217-225. (In Russ.)]. http://doi.org/10.34922/AE.2021.34.2.005 François M., Leifert W., Hecker J., Faunt J., Martins R., Thomas P., Fenech M. Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease // Cytometry A. - 2014;85(8):698-708. http://doi.org/10.1002/cyto.a.22453 François M., Leifert W., Hecker J., Faunt J., Martins R., Thomas P., Fenech M. Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease // Cytometry A. - 2014;85(8):698-708. http://doi.org/10.1002/cyto.a.22453 Syrjälä A.M., Ylöstalo P., Ruoppi P., Komulainen K., Hartikainen S., Sulkava R., Knuuttila M. Dementia and oral health among subjects aged 75 years or older // Gerodontology. - 2012;29(1):36-42. http://doi.org/10.1111/j.1741-2358.2010.00396.x Syrjälä A.M., Ylöstalo P., Ruoppi P., Komulainen K., Hartikainen S., Sulkava R., Knuuttila M. Dementia and oral health among subjects aged 75 years or older // Gerodontology. - 2012;29(1):36-42. http://doi.org/10.1111/j.1741-2358.2010.00396.x Kim J.M., Stewart R., Prince M., Kim S.W., Yang S.J., Shin I.S., Yoon J.S.. Dental health, nutritional status and recent-onset dementia in a Korean community population // Int. J. Geriatr Psychiatry. - 2007;22(9):850-855. http://doi.org/10.1002/gps.1750 Kim J.M., Stewart R., Prince M., Kim S.W., Yang S.J., Shin I.S., Yoon J.S.. Dental health, nutritional status and recent-onset dementia in a Korean community population // Int. J. Geriatr Psychiatry. - 2007;22(9):850-855. http://doi.org/10.1002/gps.1750 Stewart R., Hirani V. Dental health and cognitive impairment in an English national survey population // J. Am. Geriatr Soc. - 2007;55(9):1410-1414. http://doi.org/10.1111/j.1532-5415.2007.01298.x Stewart R., Hirani V. Dental health and cognitive impairment in an English national survey population // J. Am. Geriatr Soc. - 2007;55(9):1410-1414. http://doi.org/10.1111/j.1532-5415.2007.01298.x Sabbah W., Watt R.G., Sheiham A., Tsakos G. The role of cognitive ability in socio-economic inequalities in oral health // J. Dent Res. - 2009;88(4):351-5. http://doi.org/10.1177/0022034509334155 Sabbah W., Watt R.G., Sheiham A., Tsakos G. The role of cognitive ability in socio-economic inequalities in oral health // J. Dent Res. - 2009;88(4):351-5. http://doi.org/10.1177/0022034509334155 Zenthöfer A., Schröder J., Cabrera T., Rammelsberg P., Hassel A.J. Comparison of oral health among older people with and without dementia // Community Dent Health. - 2014;31(1):27-31. PMID: 24741890 Zenthöfer A., Schröder J., Cabrera T., Rammelsberg P., Hassel A.J. Comparison of oral health among older people with and without dementia // Community Dent Health. - 2014;31(1):27-31. PMID: 24741890 Li J., Xu H., Pan W., Wu B. Association between tooth loss and cognitive decline: A 13-year longitudinal study of Chinese older adults // PLoS One. - 2017;12(2):e0171404. http://doi.org/10.1371/journal.pone.0171404 Li J., Xu H., Pan W., Wu B. Association between tooth loss and cognitive decline: A 13-year longitudinal study of Chinese older adults // PLoS One. - 2017;12(2):e0171404. http://doi.org/10.1371/journal.pone.0171404 Tsakos G., Watt R.G., Rouxel P.L., de Oliveira C., Demakakos P. Tooth loss associated with physical and cognitive decline in older adults // J. Am. Geriatr Soc. - 2015;63(1):91-99. http://doi.org/10.1111/jgs.13190 Tsakos G., Watt R.G., Rouxel P.L., de Oliveira C., Demakakos P. Tooth loss associated with physical and cognitive decline in older adults // J. Am. Geriatr Soc. - 2015;63(1):91-99. http://doi.org/10.1111/jgs.13190 Henriksen B.M., Engedal K., Axéll T. Cognitive impairment is associated with poor oral health in individuals in long-term care // Oral Health Prev. Dent. - 2005;3(4):203-207. PMID: 16475448 Henriksen B.M., Engedal K., Axéll T. Cognitive impairment is associated with poor oral health in individuals in long-term care // Oral Health Prev. Dent. - 2005;3(4):203-207. PMID: 16475448 Olsen I., Singhrao S.K. Can oral infection be a risk factor for Alzheimer's disease? // J. Oral Microbiol. - 2015;7:29143. http://doi.org/10.3402/jom.v7.29143 Olsen I., Singhrao S.K. Can oral infection be a risk factor for Alzheimer's disease? // J. Oral Microbiol. - 2015;7:29143. http://doi.org/10.3402/jom.v7.29143 Montgomery W., Ueda K., Jorgensen M., Stathis S., Cheng Y., Nakamura T. Epidemiology, associated burden, and current clinical practice for the diagnosis and management of Alzheimer's disease in Japan // Clinicoecon Outcomes Res. - 2017;10:13-28. http://doi.org/10.2147/CEOR.S146788 Montgomery W., Ueda K., Jorgensen M., Stathis S., Cheng Y., Nakamura T. Epidemiology, associated burden, and current clinical practice for the diagnosis and management of Alzheimer's disease in Japan // Clinicoecon Outcomes Res. - 2017;10:13-28. http://doi.org/10.2147/CEOR.S146788 Иорданишвили А.К., Володин А.И., Музыкин М.И., Лапина Н.В., Самсонов В.В. Возрастные и гендерные особенности потери зубов у населения Краснодарского края. Кубанский научный медицинский вестник. 2017;24(5):31-36. [A.K. Iordanishvili, A.I. Volodin, M.I. Muzikin, N.V. Lapina, V.V. Samsonov. Age and gender features of tooth loss in the population of the Krasnodar Territory. Kuban Scientific Medical Bulletin. 2017;24(5):31-36. (In Russ.)]. https://cyberleninka.ru/article/n/vozrastnye-i-gendernye-osobennosti-poteri-zubov-u-naseleniya-krasnodarskogo-kraya Iordanishvili A.K., Volodin A.I., Muzykin M.I., Lapina N.V., Samsonov V.V. Vozrastnye i gendernye osobennosti poteri zubov u naseleniya Krasnodarskogo kraya. Kubanskiy nauchnyy medicinskiy vestnik. 2017;24(5):31-36. [A.K. Iordanishvili, A.I. Volodin, M.I. Muzikin, N.V. Lapina, V.V. Samsonov. Age and gender features of tooth loss in the population of the Krasnodar Territory. Kuban Scientific Medical Bulletin. 2017;24(5):31-36. (In Russ.)]. https://cyberleninka.ru/article/n/vozrastnye-i-gendernye-osobennosti-poteri-zubov-u-naseleniya-krasnodarskogo-kraya Chai Y.L., Chong J.R., Raquib A.R., Xu X., Hilal S., Venketasubramanian N., Tan B., Kumar A., Sethi G., Chen C.P., Lai M. Plasma osteopontin as a biomarker of Alzheimer’s disease and vascular cognitive impairment // Sci. rep. - 2021;11(1):1-11. http://doi.org/10.1038/s41598-021-83601-6 Chai Y.L., Chong J.R., Raquib A.R., Xu X., Hilal S., Venketasubramanian N., Tan B., Kumar A., Sethi G., Chen C.P., Lai M. Plasma osteopontin as a biomarker of Alzheimer’s disease and vascular cognitive impairment // Sci. rep. - 2021;11(1):1-11. http://doi.org/10.1038/s41598-021-83601-6 Comi C., Carecchio M., Chiocchetti A., Nicola S., Galimberti D., Fenoglio C., Cappellano G., Monaco F., Scarpini E., Dianzani U. Osteopontin is increased in the cerebrospinal fluid of patients with Alzheimer's disease and its levels correlate with cognitive decline // J. Alzheimer's Disease. - 2010;19(4):1143-1148. http://doi.org/10.3233/JAD-2010-1309 Comi C., Carecchio M., Chiocchetti A., Nicola S., Galimberti D., Fenoglio C., Cappellano G., Monaco F., Scarpini E., Dianzani U. Osteopontin is increased in the cerebrospinal fluid of patients with Alzheimer's disease and its levels correlate with cognitive decline // J. Alzheimer's Disease. - 2010;19(4):1143-1148. http://doi.org/10.3233/JAD-2010-1309 Rentsendorj A., Sheyn J., Fuchs D.-T. et al. A novel role for osteopontin in macrophage-mediated amyloid-β clearance in Alzheimer’s models // Brain, behave., immun. - 2018;67:163-180. https://doi.org/10.1016/j.bbi.2017.08.019 Rentsendorj A., Sheyn J., Fuchs D.-T. et al. A novel role for osteopontin in macrophage-mediated amyloid-β clearance in Alzheimer’s models // Brain, behave., immun. - 2018;67:163-180. https://doi.org/10.1016/j.bbi.2017.08.019 Sun Y., Yin X.S., Guo H, Han R.K., He R.D., Chi L.J. Elevated osteopontin levels in mild cognitive impairment and Alzheimer’s disease // Mediators inflamm. - 2013;2013(Art. ID 615745):1-9. https://doi.org/10.1155/2013/615745 Sun Y., Yin X.S., Guo H, Han R.K., He R.D., Chi L.J. Elevated osteopontin levels in mild cognitive impairment and Alzheimer’s disease // Mediators inflamm. - 2013;2013(Art. ID 615745):1-9. https://doi.org/10.1155/2013/615745 Зеленова Е.Г., Заславская М.И., Салина Е.В., Рассанов С.П. Микрофлора полости рта: норма и патология. Учебное пособие. Н. Новгород : НГМА. 2004:158. [E.G. Zelenova, M.I. Zaslavskaya, E.V. Salina, S.P. Rassanov. Oral microflora: norm and pathology. Textbook. N. Novgorod : Publishing House of NGMA. 2004:158. (In Russ.)]. https://micropspbgmu.ru/micropspbgmu/Dopolnitelnaa_literatura_files/%D0%9C%D0%B8%D0%BA%D1%80%D0%BE%D1%84%D0%BB%D0%BE%D1%80%D0%B0%20%D0%BF%D0%BE%D0%BB%D0%BE%D1%81%D1%82%D0%B8%20%D1%80%D1%82%D0%B0%20%20%D0%BD%D0%BE%D1%80%D0%BC%D0%B0%20%D0%B8%20%D0%BF%D0%B0%D1%82%D0%BE%D0%BB%D0%BE%D0%B3%D0%B8%D1%8F.pdf Zelenova E.G., Zaslavskaya M.I., Salina E.V., Rassanov S.P. Mikroflora polosti rta: norma i patologiya. Uchebnoe posobie. N. Novgorod : NGMA. 2004:158. [E.G. Zelenova, M.I. Zaslavskaya, E.V. Salina, S.P. Rassanov. Oral microflora: norm and pathology. Textbook. N. Novgorod : Publishing House of NGMA. 2004:158. (In Russ.)]. https://micropspbgmu.ru/micropspbgmu/Dopolnitelnaa_literatura_files/%D0%9C%D0%B8%D0%BA%D1%80%D0%BE%D1%84%D0%BB%D0%BE%D1%80%D0%B0%20%D0%BF%D0%BE%D0%BB%D0%BE%D1%81%D1%82%D0%B8%20%D1%80%D1%82%D0%B0%20%20%D0%BD%D0%BE%D1%80%D0%BC%D0%B0%20%D0%B8%20%D0%BF%D0%B0%D1%82%D0%BE%D0%BB%D0%BE%D0%B3%D0%B8%D1%8F.pdf Dominy S.S., Lynch C., Ermini F., Benedyk M., Marczyk A., Konradi A., Nguyen M., Haditsch U., Raha D., Griffin C., Holsinger L., Arastu-Kapur S., Kaba S., Lee A., Ryder M., Potempa B., Mydel P., Hellvard A., Adamowicz К., Hasturk H,. Walker G, Reynolds E., Faull R., Curtis M., Dragunow M., Potempa J. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors // Sci. Adv. - 2019;5(1):1-21. http://doi.org/10.1126/sciadv.aau3333 Dominy S.S., Lynch C., Ermini F., Benedyk M., Marczyk A., Konradi A., Nguyen M., Haditsch U., Raha D., Griffin C., Holsinger L., Arastu-Kapur S., Kaba S., Lee A., Ryder M., Potempa B., Mydel P., Hellvard A., Adamowicz K., Hasturk H,. Walker G, Reynolds E., Faull R., Curtis M., Dragunow M., Potempa J. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors // Sci. Adv. - 2019;5(1):1-21. http://doi.org/10.1126/sciadv.aau3333 Wingrove J.A., DiScipio R.G., Chen Z., Potempa J., Travis J., Hugli T.E. Activation of Complement Components C3 and C5 by a Cysteine Proteinase (Gingipain-1) from Porphyromonus (Bacteroides) gingivalis // J. Biol. Chem. - 1992;267(26):18902-18907. https://doi.org/10.1016/S0021-9258(19)37046-2 Wingrove J.A., DiScipio R.G., Chen Z., Potempa J., Travis J., Hugli T.E. Activation of Complement Components C3 and C5 by a Cysteine Proteinase (Gingipain-1) from Porphyromonus (Bacteroides) gingivalis // J. Biol. Chem. - 1992;267(26):18902-18907. https://doi.org/10.1016/S0021-9258(19)37046-2 Gurav A.N. Alzheimer's disease and periodontitis - an elusive link. Rev // Assoc. Med. Bras. - 2014;60(2):173-180. http://doi.org/10.1590/1806-9282.60.02.015 Gurav A.N. Alzheimer's disease and periodontitis - an elusive link. Rev // Assoc. Med. Bras. - 2014;60(2):173-180. http://doi.org/10.1590/1806-9282.60.02.015 Naorungroj S., Schoenbach V.J., Beck J., Mosley T.H., Gottesman R.F., Alonso A., Heiss G., Slade G.D. Cross-sectional associations of oral health measures with cognitive function in late middle-aged adults: a community-based study // J. Am. Dent. Assoc. - 2013;144(12):1362-1371. http://doi.org/10.14219/jada.archive.2013.0072 Naorungroj S., Schoenbach V.J., Beck J., Mosley T.H., Gottesman R.F., Alonso A., Heiss G., Slade G.D. Cross-sectional associations of oral health measures with cognitive function in late middle-aged adults: a community-based study // J. Am. Dent. Assoc. - 2013;144(12):1362-1371. http://doi.org/10.14219/jada.archive.2013.0072 Slade G.D., Ghezzi E.M., Heiss G., Beck J.D., Riche E., Offenbacher S. Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study // Arch. Intern. Med. - 2003;163(10):1172-1179. http://doi.org/10.1001/archinte.163.10.1172 Slade G.D., Ghezzi E.M., Heiss G., Beck J.D., Riche E., Offenbacher S. Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study // Arch. Intern. Med. - 2003;163(10):1172-1179. http://doi.org/10.1001/archinte.163.10.1172 Forner L., Larsen T., Kilian M., Holmstrup P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation // J Clin Periodontol. - 2006;33(6):401-407. http://doi.org/10.1111/j.1600-051X.2006.00924.x Forner L., Larsen T., Kilian M., Holmstrup P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation // J Clin Periodontol. - 2006;33(6):401-407. http://doi.org/10.1111/j.1600-051X.2006.00924.x Grammas P. Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer's disease // J. Neuroinflammation. - 2011;8:26-43. http://doi.org/10.1186/1742-2094-8-26 Grammas P. Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer's disease // J. Neuroinflammation. - 2011;8:26-43. http://doi.org/10.1186/1742-2094-8-26 Grabe H.J., Schwahn C., Völzke H., Spitzer C., Freyberger H.J., John U., Mundt T., Biffar R., Kocher T. Tooth loss and cognitive impairment // J. Clin Periodontol. - 2009;36(7):550-557. http://doi.org/10.1111/j.1600-051X.2009.01426.x Grabe H.J., Schwahn C., Völzke H., Spitzer C., Freyberger H.J., John U., Mundt T., Biffar R., Kocher T. Tooth loss and cognitive impairment // J. Clin Periodontol. - 2009;36(7):550-557. http://doi.org/10.1111/j.1600-051X.2009.01426.x Liu L., Chan C. The role of inflammasome in Alzheimer's disease // Ageing Res Rev. - 2014;15:6-15. http://doi.org/10.1016/j.arr.2013.12.007 Liu L., Chan C. The role of inflammasome in Alzheimer's disease // Ageing Res Rev. - 2014;15:6-15. http://doi.org/10.1016/j.arr.2013.12.007 Stathis S., Cheng Y., Nakamura T. Epidemiology, associated burden, and current clinical practice for the diagnosis and management of Alzheimer's disease in Japan // Clinicoecon Outcomes Res. - 2017;10:13-28. http://doi.org/10.2147/CEOR.S146788 Stathis S., Cheng Y., Nakamura T. Epidemiology, associated burden, and current clinical practice for the diagnosis and management of Alzheimer's disease in Japan // Clinicoecon Outcomes Res. - 2017;10:13-28. http://doi.org/10.2147/CEOR.S146788 Tsuneishi M., Yamamoto T., Yamaguchi T., Kodama T., Sato T. Association between number of teeth and Alzheimer’s disease using the National Database of Health Insurance Claims and Specific Health Checkups of Japan // PLoS ONE. - 2021;16(4):e0251056. https://doi.org/10.1371/journal.pone.0251056 Tsuneishi M., Yamamoto T., Yamaguchi T., Kodama T., Sato T. Association between number of teeth and Alzheimer’s disease using the National Database of Health Insurance Claims and Specific Health Checkups of Japan // PLoS ONE. - 2021;16(4):e0251056. https://doi.org/10.1371/journal.pone.0251056 Okamoto N., Morikawa M., Okamoto K., Habu N., Iwamoto J., Tomioka K., Saeki K., Yanagi M., Amano N., Kurumatani N. Relationship of tooth loss to mild memory impairment and cognitive impairment: findings from the Fujiwara-kyo study. Behav // Brain Funct. - 2010;6(77):2-8. http://doi.org/10.1186/1744-9081-6-77 Okamoto N., Morikawa M., Okamoto K., Habu N., Iwamoto J., Tomioka K., Saeki K., Yanagi M., Amano N., Kurumatani N. Relationship of tooth loss to mild memory impairment and cognitive impairment: findings from the Fujiwara-kyo study. Behav // Brain Funct. - 2010;6(77):2-8. http://doi.org/10.1186/1744-9081-6-77 Ranjan, R., Rout, M., Mishra, M., Kore, S.A. Tooth loss and dementia: An oro-neural connection. A cross-sectional study // J. Indian Society of Periodontology. - 2019;23(2):158-162. https://doi.org/10.4103/jisp.jisp_430_18 Ranjan, R., Rout, M., Mishra, M., Kore, S.A. Tooth loss and dementia: An oro-neural connection. A cross-sectional study // J. Indian Society of Periodontology. - 2019;23(2):158-162. https://doi.org/10.4103/jisp.jisp_430_18 Yoo J.J., Yoon J.H., Kang M.J., Kim M., Oh N. The effect of missing teeth on dementia in older people: a nationwide population-based cohort study in South Korea // BMC Oral Health. - 2019;19(61):2-10. https://doi.org/10.1186/s12903-019-0750-4 Yoo J.J., Yoon J.H., Kang M.J., Kim M., Oh N. The effect of missing teeth on dementia in older people: a nationwide population-based cohort study in South Korea // BMC Oral Health. - 2019;19(61):2-10. https://doi.org/10.1186/s12903-019-0750-4 Naorungroj S., Schoenbach V.J., Wruck L., Mosley T.H., Gottesman R.F., Alonso A., Heiss G., Beck J., Slade G.D. Tooth loss, periodontal disease, and cognitive decline in the Atherosclerosis Risk in Communities (ARIC) study. Community Dent // Oral Epidemiol. - 2015;43(1):47-57. http://doi.org/10.1111/cdoe.12128 Naorungroj S., Schoenbach V.J., Wruck L., Mosley T.H., Gottesman R.F., Alonso A., Heiss G., Beck J., Slade G.D. Tooth loss, periodontal disease, and cognitive decline in the Atherosclerosis Risk in Communities (ARIC) study. Community Dent // Oral Epidemiol. - 2015;43(1):47-57. http://doi.org/10.1111/cdoe.12128 Qi X., Zhu Z., Plassman B.L., Wu B. Dose-response meta-analysis on tooth loss with the risk of cognitive impairment and dementia // Journal of the American Medical Directors Association. - 2021;22(10):2039-2045. http://doi.org/10.1016/j.jamda.2021.05.009 Qi X., Zhu Z., Plassman B.L., Wu B. Dose-response meta-analysis on tooth loss with the risk of cognitive impairment and dementia // Journal of the American Medical Directors Association. - 2021;22(10):2039-2045. http://doi.org/10.1016/j.jamda.2021.05.009