Влияние ингибиторов протонной помпы на когнитивные функции и риск деменции

Остроумова О.Д., Переверзев А.П. Влияние ингибиторов протонной помпы на когнитивные функции и риск деменции. Consilium Medicum. 2019; 21 (2): 31–36. DOI: 10.26442/20751753.2019.2.180171

________________________________________________

Ostroumova O.D., Pereverzev A.P. Influence of proton pump inhibitors on cognitive function and dementia risk. Consilium Medicum. 2019; 21 (2): 31–36. DOI: 10.26442/20751753.2019.2.180171

Читать PDF

Аннотация

Начиная со 2-й половины XX в. во всем мире наблюдается изменение возрастной структуры населения с постоянным увеличением в популяции доли людей пожилого и старческого возраста, что обусловливает актуальность профилактики и лечения большого количества возраст-ассоциированных заболеваний, в том числе неврологических. Одним из возможных факторов риска развития деменции и болезни Альцгеймера является прием ингибиторов протонной помпы (ИПП). Авторами проведен поиск и анализ данных о связи между приемом ИПП и развитием деменции, результат которого представлен в данной статье. Выявлено, что ИПП могут влиять на продукцию b-амилоида, они изменяют активность b-секретазы 1 и g-секретазы – двух ферментов, отвечающих за деградацию белка-предшественника b-амилоида, что приводит к увеличению образования b-амилоида. Также показано, что развитие когнитивных нарушений при приеме ИПП может быть опосредовано дефицитом витамина В12. На основании полученных данных с целью разработки предложения по снижению риска развития когнитивных нарушений и деменции у пациентов с сопутствующими факторами риска проведен анализ физико-химических свойств различных ИПП, который позволил выделить пантопразол как один из наиболее оптимальных препаратов для лечения заболеваний желудочно-кишечного тракта у пациентов, имеющих высокий риск возникновения/прогрессирования когнитивных нарушений и деменции.

Ключевые слова: ингибиторы протонной помпы, пантопразол, когнитивные нарушения, деменция, болезнь Альцгеймера.

________________________________________________

During the last half of the 20th century change of population age structure with constant increase of elderly and senior age population is observed all over the world. It determines the importance of prevention and treatment of great number of age-associated diseases including neurological ones. Proton pump inhibitors (PPI) use is one of possible risk factors for dementia and Alzheimer's disease development. The authors have performed research and data analysis on association of PPI use and dementia development. Acquired results are presented in the article. It has been shown that PPI use may influence b-amyloid production as they change b-secretase 1 and g-secretase activity – the enzymes responsible for b-amyloid precursor protein degradation, that results in increase of b-amyloid production. It was also demonstrated that cognitive impairment development in PPI use may be mediated by vitamin B12 deficit. Also the authors performed analysis of different PPI physical and chemical properties in order to develop suggestions on cognitive impairment risk decrease in patients with contributing risk factors. The performed analysis allowed to identify pantoprazole as one of the most appropriate medications for gastrointestinal disease treatment in patients with high risk of cognitive impairment and dementia development/progression.

Key words: proton pump inhibitor, pantoprazole, cognitive impairment, dementia, Alzheimer's disease.

Полный текст

Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.

Список литературы

1. Яхно Н.Н., Захаров В.В., Локшина А.Б. и др. Деменции: руководство для врачей. Изд. 3-е. М.: МЕДпреcс-информ, 2011.
[Iakhno N.N., Zakharov V.V., Lokshina A.B. et al. Dementsii: rukovodstvo dlia vrachei. Izd. 3-e. Moscow: MEDprecs-inform, 2011 (in Russian).]
2. Nevado-Holgado AJ, Kim CH, Winchester L et al. Commonly prescribed drugs associate with cognitive function: a cross-sectional study in UK Biobank. BMJ Open 2016; 6 (11): e012177. DOI: 10.1136/bmjopen-2016-012177
3. Ferri CP, Prince M, Brayne C et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366 (9503): 2112–7. DOI: 10.1016/S0140-6736(05)67889-0
4. Yuan M, Xie X, Cao WF et al. Proton Pump Inhibitors and the Risk of Dementia: is There a Link? Med Princ Pract 2018. DOI: 10.1159/000494461
5. Imfeld P, Bodmer M, Jick SS, Meier CR. Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis. Drug Saf 2018. DOI: 10.1007/s40264-018-0704-9
6. Eusebi LH, Rabitti S, Artesiani ML et al. Proton pump inhibitors: Risks of long-term use. J Gastroenterol Hepatol 2017; 32 (7): 1295–1302. DOI: 10.1111/jgh.13737
7. Gomm W, von Holt K, Thome F et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol 2016; 73: 410–16.
8. Ortiz-Guerrero G, Amador-Muñoz D, Calderón-Ospina CA et al. Proton Pump Inhibitors and Dementia: Physiopathological Mechanisms and Clinical Consequences. Neural Plast 2018; 2018: 5257285. DOI: 10.1155/2018/5257285
9. Delgado MG, Calleja S, Suarez L, Pascual J. Recurrent confusional episodes associated with hypomagnesaemia due to esomeprazol. BMJ Case Reports 2013; article bcr2013200501.
10. Pasina L, Zanotta D, Puricelli S, Bonoldi G. Acute neurological symptoms secondary to hypomagnesemia induced by proton pump inhibitors: a case series. Eur J Clin Pharmacol 2016; 72 (5): 641–3.
11. Herghelegiu AM, Prada GI, Nacu R. Prolonged use of proton pomp inhibitors and cognitive function in older adults. Farmácia 2016; 64 (2): 262–7.
12. Booker A, Jacob L.E, Rapp M et al. Risk factors for dementia diagnosis in German primary care practices. Int Psychogeriatrics 2016; 28 (7): 1059–65.
13. Haenisch B, von Holt K, Wiese B et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci 2015; 265: 419–28.
14. Gray SL, Walker RL, Dublin S et al. Proton Pump Inhibitor Use and Dementia Risk: Prospective Population-Based Study. J Am Geriatr Soc 2018; 66 (2): 247–253. DOI: 10.1111/jgs.15073
15. Tai SY, Chien CY, Wu DC et al. Risk of dementia from proton pump inhibitor use in Asian population: a nationwide cohort study in Taiwan. PLoS One 2017; 12 (2): e0171006.
16. Batchelor R, Gilmartin JF, Kemp W et al. Dementia, cognitive impairment and proton pump inhibitor therapy: A systematic review. J Gastroenterol Hepatol 2017; 32 (8): 1426–35. DOI: 10.1111/jgh.13750
17. Badiola N, Alcalde V, Pujol A et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One 2013; 8 (3): e58837. DOI: 10.1371/journal.pone.0058837
18. Sigaroudi A, Stelzer C, Braun T et al. Comparison of pantoprazole concentrations in simultaneous cerebrospinal fluid and serum samples. Conference Paper 16. Jahrekongress Klinische Pharmakologie. 2014. Available at: https://www.researchgate.net/publication/267651610_Comparison_of_pantoprazolp_concentrations_in_simu...
19. Государственный реестр лекарственных средств. http://grls.rosminzdrav.ru
[Gosudarstvennyi reestr lekarstvennykh sredstv. http://grls.rosminzdrav.ru (in Russian).]
20. База данных лекарственных средств DrugBank. https://www.drugbank.ca
[Baza dannykh lekarstvennykh sredstv DrugBank. https://www.drugbank.ca (in Russian).]
21. Информационно-вспомогательная система Medscape. https://reference.medscape.com
[Informatsionno-vspomogatel'naia sistema Medscape. https://reference.medscape.com (in Russian).]
22. Dombrower P. Pantoprazole: a new proton-pump inhibitor. J Pharm Pract 1999; 12 (6).
23. Akter S, Hassan MR, Shahriar M et al. Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software. Alzheimers Res Ther 2015; 7: 79. DOI: 10.1186/s13195-015-0164-8
24. Fallahzadeh MK, Borhani Haghighi A, Namazi MR. Proton pump inhibitors: predisposers to Alzheimer disease? J Clin Pharm Ther 2010; 35: 125–6.
25. Majumdar A, Capetillo-Zarate E, Cruz D et al. Degradation of Alzheimer’s amyloid fibrils by microglia requires delivery of ClC-7 to lysosomes. Mol Biol Cell 2011; 22: 1664–76.
26. Chiarini A, Dal Pra I, Whitfield JF, Armato U. The killing of neurons by b-amyloid peptides, prions, and pro-inflammatory cytokines. Ital J Anat Embryol 2006; 111: 221–46.
27. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 2013; 310: 2435–42.
28. Heidelbaugh JJ. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf 2013; 4: 125–33.
29. Hammel I, Agarwal R, Manandhar L et al. Effects of long-term proton pump inhibitors on the quantitative levels of vitamin B12: an observational study. Biol Biomed Rep 2012; 2: 230–3.
30. O’Leary F, Allman-Farinelli M, Samman S. Vitamin B12 status, cognitive decline and dementia: a systematic review of prospective cohort studies. Br J Nutr 2012; 108: 1948–61.
31. Smith AD, Refsum H. Vitamin B12 and cognition in the elderly. Am J Clin Nutr 2009; 89: 707S–11.
32. Vogiatzoglou A, Smith AD, Nurk E et al. Cognitive function in an elderly population: interaction between vitamin B12 status, depression, and apolipoprotein E ε4: the Hordaland Homocysteine Study. Psychosom Med 2013; 75: 20–9.
33. Wang HX, Wahlin A, Basun H et al. Vitamin B12 and folate in relation to the development of Alzheimer’s disease. Neurology 2001; 56: 1188–94.
34. Hooshmand B, Solomon A, Kåreholt I et al. Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study. Neurology 2010; 75: 1408–14.
35. Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull 2008; 29: 143–72.
36. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol 2006; 5: 949–60.
37. McCracken C, Hudson P, Ellis R, McCaddon A. Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study. Am J Clin Nutr 2006; 84: 1406–11.
38. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ 2008; 336: 2–3.
39. Naunton M, Peterson GM, Bleasel MD. Overuse of proton pump inhibitors. J Clin Pharm Ther 2000; 25: 333–40.
40. Walker NM, McDonald J. An evaluation of the use of proton pump inhibitors. Pharm World Sci 2001; 23: 116–7.
41. Grant K, Al-Adhami N, Tordoff J et al. Continuation of proton pump inhibitors from hospital to community. Pharm World Sci 2006; 28: 189–93.
42. Batuwitage BT, Kingham JGC, Morgan NE, Bartlett RL. Inappropriate prescribing of proton pump inhibitors in primary care. Postgrad Med J 2007; 83: 66–8.
43. Heidelbaugh JJ, Goldberg KL, Inadomi JM. Magnitude and economic impact of overutilization of antisecretory therapy in the ambulatory care setting. Am J Manag Care 2010; 16: e228–34.

________________________________________________

1. Iakhno N.N., Zakharov V.V., Lokshina A.B. et al. Dementsii: rukovodstvo dlia vrachei. Izd. 3-e. Moscow: MEDprecs-inform, 2011 (in Russian).
2. Nevado-Holgado AJ, Kim CH, Winchester L et al. Commonly prescribed drugs associate with cognitive function: a cross-sectional study in UK Biobank. BMJ Open 2016; 6 (11): e012177. DOI: 10.1136/bmjopen-2016-012177
3. Ferri CP, Prince M, Brayne C et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366 (9503): 2112–7. DOI: 10.1016/S0140-6736(05)67889-0
4. Yuan M, Xie X, Cao WF et al. Proton Pump Inhibitors and the Risk of Dementia: is There a Link? Med Princ Pract 2018. DOI: 10.1159/000494461
5. Imfeld P, Bodmer M, Jick SS, Meier CR. Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis. Drug Saf 2018. DOI: 10.1007/s40264-018-0704-9
6. Eusebi LH, Rabitti S, Artesiani ML et al. Proton pump inhibitors: Risks of long-term use. J Gastroenterol Hepatol 2017; 32 (7): 1295–1302. DOI: 10.1111/jgh.13737
7. Gomm W, von Holt K, Thome F et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol 2016; 73: 410–16.
8. Ortiz-Guerrero G, Amador-Muñoz D, Calderón-Ospina CA et al. Proton Pump Inhibitors and Dementia: Physiopathological Mechanisms and Clinical Consequences. Neural Plast 2018; 2018: 5257285. DOI: 10.1155/2018/5257285
9. Delgado MG, Calleja S, Suarez L, Pascual J. Recurrent confusional episodes associated with hypomagnesaemia due to esomeprazol. BMJ Case Reports 2013; article bcr2013200501.
10. Pasina L, Zanotta D, Puricelli S, Bonoldi G. Acute neurological symptoms secondary to hypomagnesemia induced by proton pump inhibitors: a case series. Eur J Clin Pharmacol 2016; 72 (5): 641–3.
11. Herghelegiu AM, Prada GI, Nacu R. Prolonged use of proton pomp inhibitors and cognitive function in older adults. Farmácia 2016; 64 (2): 262–7.
12. Booker A, Jacob L.E, Rapp M et al. Risk factors for dementia diagnosis in German primary care practices. Int Psychogeriatrics 2016; 28 (7): 1059–65.
13. Haenisch B, von Holt K, Wiese B et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci 2015; 265: 419–28.
14. Gray SL, Walker RL, Dublin S et al. Proton Pump Inhibitor Use and Dementia Risk: Prospective Population-Based Study. J Am Geriatr Soc 2018; 66 (2): 247–253. DOI: 10.1111/jgs.15073
15. Tai SY, Chien CY, Wu DC et al. Risk of dementia from proton pump inhibitor use in Asian population: a nationwide cohort study in Taiwan. PLoS One 2017; 12 (2): e0171006.
16. Batchelor R, Gilmartin JF, Kemp W et al. Dementia, cognitive impairment and proton pump inhibitor therapy: A systematic review. J Gastroenterol Hepatol 2017; 32 (8): 1426–35. DOI: 10.1111/jgh.13750
17. Badiola N, Alcalde V, Pujol A et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One 2013; 8 (3): e58837. DOI: 10.1371/journal.pone.0058837
18. Sigaroudi A, Stelzer C, Braun T et al. Comparison of pantoprazole concentrations in simultaneous cerebrospinal fluid and serum samples. Conference Paper 16. Jahrekongress Klinische Pharmakologie. 2014. Available at: https://www.researchgate.net/publication/267651610_Comparison_of_pantoprazolp_concentrations_in_simu...
19. Gosudarstvennyi reestr lekarstvennykh sredstv. http://grls.rosminzdrav.ru (in Russian).
20. Baza dannykh lekarstvennykh sredstv DrugBank. https://www.drugbank.ca (in Russian).
21. Informatsionno-vspomogatel'naia sistema Medscape. https://reference.medscape.com (in Russian).
22. Dombrower P. Pantoprazole: a new proton-pump inhibitor. J Pharm Pract 1999; 12 (6).
23. Akter S, Hassan MR, Shahriar M et al. Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software. Alzheimers Res Ther 2015; 7: 79. DOI: 10.1186/s13195-015-0164-8
24. Fallahzadeh MK, Borhani Haghighi A, Namazi MR. Proton pump inhibitors: predisposers to Alzheimer disease? J Clin Pharm Ther 2010; 35: 125–6.
25. Majumdar A, Capetillo-Zarate E, Cruz D et al. Degradation of Alzheimer’s amyloid fibrils by microglia requires delivery of ClC-7 to lysosomes. Mol Biol Cell 2011; 22: 1664–76.
26. Chiarini A, Dal Pra I, Whitfield JF, Armato U. The killing of neurons by b-amyloid peptides, prions, and pro-inflammatory cytokines. Ital J Anat Embryol 2006; 111: 221–46.
27. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 2013; 310: 2435–42.
28. Heidelbaugh JJ. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf 2013; 4: 125–33.
29. Hammel I, Agarwal R, Manandhar L et al. Effects of long-term proton pump inhibitors on the quantitative levels of vitamin B12: an observational study. Biol Biomed Rep 2012; 2: 230–3.
30. O’Leary F, Allman-Farinelli M, Samman S. Vitamin B12 status, cognitive decline and dementia: a systematic review of prospective cohort studies. Br J Nutr 2012; 108: 1948–61.
31. Smith AD, Refsum H. Vitamin B12 and cognition in the elderly. Am J Clin Nutr 2009; 89: 707S–11.
32. Vogiatzoglou A, Smith AD, Nurk E et al. Cognitive function in an elderly population: interaction between vitamin B12 status, depression, and apolipoprotein E ε4: the Hordaland Homocysteine Study. Psychosom Med 2013; 75: 20–9.
33. Wang HX, Wahlin A, Basun H et al. Vitamin B12 and folate in relation to the development of Alzheimer’s disease. Neurology 2001; 56: 1188–94.
34. Hooshmand B, Solomon A, Kåreholt I et al. Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study. Neurology 2010; 75: 1408–14.
35. Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull 2008; 29: 143–72.
36. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol 2006; 5: 949–60.
37. McCracken C, Hudson P, Ellis R, McCaddon A. Methylmalonic acid and cognitive function in the Medical Research Council Cognitive Function and Ageing Study. Am J Clin Nutr 2006; 84: 1406–11.
38. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ 2008; 336: 2–3.
39. Naunton M, Peterson GM, Bleasel MD. Overuse of proton pump inhibitors. J Clin Pharm Ther 2000; 25: 333–40.
40. Walker NM, McDonald J. An evaluation of the use of proton pump inhibitors. Pharm World Sci 2001; 23: 116–7.
41. Grant K, Al-Adhami N, Tordoff J et al. Continuation of proton pump inhibitors from hospital to community. Pharm World Sci 2006; 28: 189–93.
42. Batuwitage BT, Kingham JGC, Morgan NE, Bartlett RL. Inappropriate prescribing of proton pump inhibitors in primary care. Postgrad Med J 2007; 83: 66–8.
43. Heidelbaugh JJ, Goldberg KL, Inadomi JM. Magnitude and economic impact of overutilization of antisecretory therapy in the ambulatory care setting. Am J Manag Care 2010; 16: e228–34.

Авторы

О.Д.Остроумова*, А.П.Переверзев

ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России – ОСП «Российский геронтологический научно-клинический центр», Москва, Россия
*ostroumova.olga@mail.ru

________________________________________________

Olga D. Ostroumova*, Anton P. Pereverzev

Pirogov Russian National Research Medical University – Russian Clinical and Research Center of Gerontology, Moscow, Russia
*ostroumova.olga@mail.ru

Назад к списку

Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.