Table 1.

Studies that observed the effects of PPIs on dementia or Alzheimer’s disease

No.	Study (first author/year)	Country	Type of study	Study setting	No. of patients	Study period	Result
1	Xie K, 2024	China	Observational study	GWAS database	46 261	-	No link found between PPI use and dementia
2	Wu B, 2024	China	Observational study for Pharmacovigilance	US FDA AERS database	776 191	2004–2023	The authors identified a significant association between dementia and PPIs, except Vonoprazan and Tegoprazan, especially taking competition bias into account.
3	Pourhadi N, 2024	Denmark	Observational study	General population in Denmark	1 983 785	2000–2018	PPI use had no effect on the development of dementia if dementia onset is >90 years of age
4	Khan Z, 2024	India	Secondary research study	SAIL Databank, Wales	183 968	1999–2015	Chronic PPI use can conceal underlying conditions, including cancer, celiac disease, vitamin B12 deficiency, and renal injury, highlighting dementia risk and the need for further investigations on cognitive health
5	Northuis C, 2023	USA	Observational Study	Community-based cohort in the US	5712 dementia-free patients	1987–1989/follow-up from 2006 to 2011	With a minimum cumulative use of PPIs at 111 days and the maximum at 20.3 years, this study Class III evidence that the use of prescribed PPIs for >4.4 years by individuals aged 45 years and older is associated with a higher incidence of newly diagnosed dementia.
6	Mehta R, 2023	USA	Observational cohort study	Community-based cohort in the US and Australia	18 934	2010–2014	The authors found no association between acid suppression and incident dementia, cognitive impairment, and even decline in cognitive function scores over time
7	Zhang P, 2022	China	Experimental study	UK Biobank	501 002	2006–2010	The finding of this large population-based cohort study indicates that the use of proton pump inhibitors is associated with an increased risk of incident dementia, particularly among APOE ε4 heterozygotes.
8	Azhar M, 2021	USA	Secondary research study	Review	-	-	Review suggesting that the association between PPI use and dementia is more cause for alarm than reassurance but treatment plans have to be customized for each patient.
9	Li M, 2019	China	Systematic review	Review of cohort studies	73 679	2019	No statistical association between PPI use and increased risk of dementia or AD.
10	Song Y, 2019	China	Systematic review	Review	642 305	Studies published up to 2018	The current evidence indicates that PPI use does not increase dementia and AD risk
11	Imfeld P, 2018	Switzerland	Observational case control study	Clinical Practice Research Datalink	82 058	19982015	In this large, case-control analysis, the authors did not find any evidence for an increased risk of either AD or VaD related to PPI or H2RA use.
12	Gray S, 2018	USA	Observational cohort study	Kaiser Permanente, Washington	3484	Follow-up period of 7.5 years	Proton pump inhibitor use was not associated with dementia risk, even for people with high cumulative exposure.
13	Tai S, 2017	Taiwan	Observational cohort study	Nationwide study in Taiwan	15 726	2000–2003	Cumulative PPI use was significantly associated with dementia.