Table 1.
Clinical studies characteristics of long-term PPI use and dementia risk findings.
| S. No. | Study Title | Study Design | Sample Size (PPI/Non-PPI) | Duration of PPI | Key Findings |
|---|---|---|---|---|---|
| 1. | Bonomini et al., 2015 [100] | Prospective cohort | 13,864 patients | 9-14 years follow up | Unable to find convincing evidence of PPI-associated dementia risks in the study |
| 2. | Miller, 2018 [123] | Retrospective cohort | 36,360 (PPI) 99,362 (Non-PPI) |
13 years | Observations indicate a slight increase in the risk of non-AD dementia. |
| 3. | Moledina and Perazella, 2016 [21] | Prospective cohort | 2950 (PPI) 70,729 (Non-PPI) |
5.4 years | Found statistical link between the use of PPI and risk of dementia |
| 4. | Torres -Bondia et al., 2020 [124] | Retrospective cohort | 7342 (PPI) | 3 years | An increased risk of PPI-associated dementia was found |
| 5. | Park et al., 2018 [125] | Retrospective cohort | 6584 (PPI) | 5 years | PPI users found at higher risk of dementia |
| 6. | Chen et al., 2020 [126] | Retrospective cohort | 11828 (PPI) 11828 (Non-PPI) |
10 years | A significant association between PPI users and dementia was found |
| 7. | Zhang et al., 2022 [12] | Retrospective cohort | 183,968 (PPI) 131110 (Non-PPI) |
10.9 years | Unable to find the link between the use of PPI and increased dementia risk |
| 8. | O’Brien and Wong, 2011 [27] | Prospective study | 402 (PPI) 3082 (Non-PPI) |
7.5 years | PPI was not found to be linked with the risk of dementia |
| 9. | Welu et al., 2019 [127] | Retrospective cohort | 10,533 (PPI) | 5 years | PPI was not significantly found to increase the dementia risk |
| 10. | Huang et al., 2019 [128] | Multicenter double-blind, randomized controlled trial | 8791 (PPI) 8807 (Placebo) |
3 years | No association between PPI and dementia was found |
| 11. | Moayyedi et al. 2019 [129] | Prospective cohort |
LSADT cohort 299 (PPI) 3316 (Non-PPI) MADT cohort 262 (PPI) 4001 (Non-PPI) |
2-10 years follow up | No link was found between chronic PPI use and cognitive score or decline. |
| 12. | Cooksey et al., 2020 [13] | Prospective cohort | Cases: 2505, including 932 (AD), 524 vascular dementia (VaD) | 9 years | Chronic use of PPI was found to be associated with incident dementia |
| 13. | Varghese et al., 2022 [11] | Meta-analysis | 6 cohort study | 0.67-9 years follow up | PPI was not significantly associated with dementia |
| 14. | Wod et al., 2018 [130] | Observational longitudinal study | 884 (Always PPI user) 1925 (Intermittent PPI user) 7677 (Non-PPI user) |
10 years | PPI use was linked with lower cognitive function decline risk |
| 15. | Goldstein et al., 2017 [131] | Meta-analysis of 11 observational studies | 158,954 (PPI users) 483,995 (Non-PPI) | 5-10 years | No evidence has been discovered to be linked between PPI and increased dementia risk. |
Note: The given table collects data from a variety of clinical studies looking into the link between long-term PPI use and dementia. The research uses a variety of designs, including multicenter double-blind, randomized controlled trials, prospective and retrospective cohorts, and meta-analyses. Participants in the studies used PPIs for durations ranging from about 2 to 14 years, and the sample sizes were widely dispersed. The primary findings are inconsistent; although certain research indicates a greater chance of dementia associated with PPI use, other studies find no conclusive evidence of a significant correlation, if any, between PPI use and dementia risk. These conflicting findings highlight the need for additional investigation into the possible causes of the association between PPI usage and dementia. Abbreviations: PPI: proton-pump inhibitor, AD: Alzheimer’s disease, VaD: vascular dementia, LSADT: Longitudinal Study of Aging Danish Twins, MADT: Middle-Aged Danish Twin study.