Observational studies |
Results |
ACD: HR=1.38; 95%CI (1.04–1.8); AD: HR=1.44; 95%CI (1.01–2.06) |
HR=1.44; 95%CI (1.36–1.52) (p<0.001) |
From normal cognition: HR=0.78; 95%CI (0.66–0.93) (p=0.005)Progression from MCI to Dementia: HR=0.82; 95%CI (0.69–0.98) (p=0.03) |
ACD: OR=1.13 (p=0.67)AD: OR=1.11 (p=0.77). Cumulative doses of: 365 TSDDs, 1,095 TSDDs and 1,825 TSDDs: HRs without statistical significance. |
Mean score differences from 0.00 to −0.06 points for periods of PPI use between 1 to 14 years. p≥0.84 |
HR=0.99, 95%CI (0.70–1.37) |
Dementia diagnosis: aSR=1.21;95%CI (1.16–1.27). Use of anti-dementia drugs: aSR=1.38 95%CI (1.28–1.48) |
Elderly PPI users vs. non-users: difference of −1.22 points, 95%CI (−3.73–1.29) Individuals 46-67 years old PPI users vs. non-users: difference of 0.94 points, 95%CI (−1.63–3.50) |
Prolonged use of PPIs: HR=0.99, 95%CI (0.93–1.17) Intermittent use of PPIs: HR=0.91, 95%CI (0.76–1.09) |
Outcome |
Diagnosis of all-cause dementia or Alzheimer's disease |
Dementia diagnosis |
Diagnosis of LBD (Lewy Bodies Dementia)Dementia from normal cognition or diagnosis of dementia in patients with LBD. |
Diagnosis of all-cause dementia or Alzheimer's disease |
Neurocognitive assessment performance |
Dementia diagnosis |
Dementia diagnosis or prescription of anti-dementia drugs |
Neurocognitive assessment performance |
Dementia diagnosis |
Intervention |
PPIs use |
PPIs use |
PPIs use |
PPIs use (cumulative dose) |
PPIs use |
Cumulative dose PPIs vs. H2 blockers |
PPIs use |
PPIs use |
PPIs use |
Sample |
3,076 |
73,679 |
10,486 |
3,484 |
13,864 |
70,529 |
1,000,000 |
7,878 |
10,533 |
Type of study |
Prospective cohort |
Prospective cohort |
Retrospective cohort |
Prospective cohort |
Prospective cohort |
Prospective cohort |
Retrospective cohort |
Prospective cohort |
Retrospective cohort |
Author, Year |
Haenisch et al.1414 Haenisch B, von Holt K, Wiese B, Prokein J, Lange C, Ernst A, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):419-28. https://doi.org/10.1007/s00406-014-0554-0 https://doi.org/10.1007/s00406-014-0554-...
, 2015 |
Gomm et al.1515 Gomm W, von Holt K, Thomé F, Broich K, Maier W, Fink A, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-6. https://doi.org/10.1001/jamaneurol.2015.4791 https://doi.org/10.1001/jamaneurol.2015....
, 2016 |
Goldstein et al.3535 Goldstein FC, Steenland K, Zhao L, Wharton W, Levey AI, Hajjar I. Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc. 2017;65(9):1969-74. https://doi.org/10.1111/jgs.14956 https://doi.org/10.1111/jgs.14956...
, 2017 |
Gray et al.2828 Lochhead P, Hagan K, Joshi AD, Khalili H, Nguyen LH, Grodstein F, et al. Association between proton pump inhibitor use and cognitive function in women. Gastroenterology. 2017;153(4):971-9.e4. https://doi.org/10.1053/j.gastro.2017.06.061 https://doi.org/10.1053/j.gastro.2017.06...
, 2017 |
Lochhead et al.2727 Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157(3):682-91.e2. https://doi.org/10.1053/j.gastro.2019.05.056 https://doi.org/10.1053/j.gastro.2019.05...
, 2017 |
Hwang et al.3030 Hwang IC, Chang J, Park SM. A nationwide population-based cohort study of dementia risk among acid suppressant users. Am J Geriatr Psychiatry. 2018;26(11):1175-83. https://doi.org/10.1016/j.jagp.2018.06.002 https://doi.org/10.1016/j.jagp.2018.06.0...
, 2018 |
Park et al.3131 Park SK, Baek YH, Pratt N, Ellett LL, Shin JY. The uncertainty of the association between proton pump inhibitor use and the risk of dementia: prescription sequence symmetry analysis using a Korean healthcare database between 2002 and 2013. Drug Saf. 2018;41(6):615-24. https://doi.org/10.1007/s40264-018-0638-2 https://doi.org/10.1007/s40264-018-0638-...
, 2018 |
Wod et al.2929 Wod M, Hallas J, Andersen K, Rodríguez LAG, Christensen K, Gaist D. Lack of association between proton pump inhibitor use and cognitive decline. Clin Gastroenterol Hepatol. 2018;16(5):681-9. https://doi.org/10.1016/j.cgh.2018.01.034 https://doi.org/10.1016/j.cgh.2018.01.03...
, 2018 |
Huang et al.3737 Huang ST, Tseng LY, Chen LK, Peng LN, Hsiao FY. Does long-term proton pump inhibitor use increase risk of dementia? Not really! Results of the group-based trajectory analysis. Clin Pharmacol Ther. 2019;106(3):616-22. https://doi.org/10.1002/cpt.1430 https://doi.org/10.1002/cpt.1430...
, 2019 |
Observational studies |
LE |
II |
II |
II |
II |
II |
II |
II |
II |
II |
II |
Conclusion |
No association |
Increased risk |
Increased risk |
Risk reduction |
Increased risk |
No association |
No association |
Risk reduction |
No association |
No association |
Results |
IRR=1.01;95%CI (0.96–1.06) |
OR=1.55 (p<0.001) |
aHR=1.42;95%CI (1.07–1.84) Association between cumulative dose and risk of dementia with statistical significance (p-trend<0.001) |
HR=0.67, 95%CI (0.65–0.67)(p<0.01) |
AD: aOR=1.06;95%CI (0.93–1.21)nAD: aOR=1.20, 95%CI (1.05–1.37)(p=0.007). AD for high dose PPI: aOR=1.20; 95%CI (0.91–1.61)nAD for high dose PPI: aOR=0.95, 95%CI (0.74–1.22) |
aHR=0.72;95%CI (0.51–1.03) |
aOR=1,0; 95%CI (0,40–2,73) |
OR=0.93, CI95% (0.90–0.97)(p=0.0008) |
aOR=1.01;95%CI (0.97–1.06) |
AD: aOR=0.88; 95%CI (0.80–0.97)VV: aOR=1.18, 95%CI (1.04–1.33) |
Outcome |
Dementia diagnosis |
Dementia diagnosis or prescription of anti-dementia drugs |
Dementia diagnosis |
Dementia diagnosis |
Diagnosis of Alzheimer's disease or non-Alzheimer dementia |
Dementia diagnosis |
Dementia diagnosis |
Dementia diagnosis |
Alzheimer's Disease Diagnosis |
Development of Alzheimer's Disease or Vascular Dementia |
Intervention |
PPIs use |
PPIs use |
PPIs use (cumulative dose) |
PPIs use |
PPIs use |
PPIs use (and H2 blockers) |
Continuous PPIs’ use |
PPIs use |
PPIs use (cumulative dose) |
PPIs use |
Sample |
304,753 |
23,656 |
62,574 |
315,078 |
135,722 |
92,773 |
7,8 billion |
23,912 (1:1) |
353,576 (1:4) |
41,029 |
Type of study |
Retrospective cohort |
Retrospective cohort |
Retrospective cohort |
Retrospective cohort |
Retrospective cohort |
Retrospective cohort |
Cross-sectional |
Case control |
Case control |
Case control |
Author, Year |
Park et al.3636 Park SK, Nam JH, Lee H, Chung H, Lee EK, Shin JY. Beyond uncertainty: negative findings for the association between the use of proton pump inhibitors and risk of dementia. J Gastroenterol Hepatol. 2019;34(12):2135-43. https://doi.org/10.1111/jgh.14745 https://doi.org/10.1111/jgh.14745...
, 2019 |
Welu et al.3232 Welu J, Metzger J, Bebensee S, Ahrendt A, Vasek M. Proton pump inhibitor use and risk of dementia in the veteran population. Fed Pract. 2019;36(Suppl 4):S27-S31. PMID: 31296980, 2019 |
Chen et al.3333 Chen LY, Lin HJ, Wu WT, Chen YC, Chen CL, Kao J, et al. Clinical use of acid suppressants and risk of dementia in the elderly: a pharmaco-epidemiological cohort study. Int J Environ Res Public Health. 2020;17(21):8271. https://doi.org/10.3390/ijerph17218271 https://doi.org/10.3390/ijerph17218271...
, 2020 |
Cooksey et al.3434 Cooksey R, Kennedy J, Dennis MS, Escott-Price V, Lyons RA, Seaborne M, et al. Proton pump inhibitors and dementia risk: evidence from a cohort study using linked routinely collected national health data in Wales, UK. PLoS One. 2020;15(9):e0237676. https://doi.org/10.1371/journal.pone.0237676 https://doi.org/10.1371/journal.pone.023...
, 2020 |
Torres-Bondia et al.1616 Torres-Bondia F, Dakterzada F, Galván L, Buti M, Besanson G, Gill E, et al. Proton pump inhibitors and the risk of Alzheimer's disease and non-Alzheimer's dementias. Sci Rep. 2020;10(1):21046. https://doi.org/10.1038/s41598-020-78199-0 https://doi.org/10.1038/s41598-020-78199...
, 2020 |
Wu et a.l3838 Wu CL, Lei WY, Wang JS, Lin CE, Chen CL, Wen SH. Acid suppressants use and the risk of dementia: a population-based propensity score-matched cohort study. PLoS One. 2020;15(11):e0242975. https://doi.org/10.1371/journal.pone.0242975 https://doi.org/10.1371/journal.pone.024...
, 2020 |
Ma et al.4242 Ma C, Shaheen AA, Congly SE, Andrews CN, Moayyedi P, Forbes N. Interpreting reported risks associated with use of proton pump inhibitors: residual confounding in a 10-year analysis of national ambulatory data. Gastroenterology. 2020;158(3):780-2.e3. https://doi.org/10.1053/j.gastro.2019.10.023 https://doi.org/10.1053/j.gastro.2019.10...
, 2020 |
Booker et al.4141 Booker A, Jacob LE, Rapp M, Bohlken J, Kostev K. Risk factors for dementia diagnosis in German primary care practices. Int Psychogeriatr. 2016;28(7):1059-65. https://doi.org/10.1017/S1041610215002082 https://doi.org/10.1017/S104161021500208...
, 2016 |
Taipale et al.4040 Taipale H, Tolppanen AM, Tiihonen M, Tanskanen A, Tiihonen J, Hartikainen S. No association between proton pump inhibitor use and risk of Alzheimer's disease. Am J Gastroenterol. 2017;112(12):1802-8. https://doi.org/10.1038/ajg.2017.196 https://doi.org/10.1038/ajg.2017.196...
, 2017 |
Imfeld et al.3939 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;41(12):1387-96. https://doi.org/10.1007/s40264-018-0704-9 https://doi.org/10.1007/s40264-018-0704-...
, 2018 |