What does the evidence actually show about PPIs and dementia?
The research is genuinely split. Several large, well-conducted studies find a link between long-term PPI use and a higher chance of developing dementia. For instance, a 2023 analysis of over 5,700 older adults in the ARIC study found that those who used PPIs for more than 4.4 years had a 33% higher risk of developing dementia compared to non-users [2][10]. Another massive German study of nearly 2.7 million people reported that starting a PPI was associated with a 54% higher risk of dementia [4]. A nationwide Danish study of almost 2 million people also found a 36% higher rate of dementia in PPI users aged 60-69, though the risk was smaller in older age groups [9].
However, other equally rigorous studies contradict this. A 2022 Canadian cohort that followed patients for up to 22 years found that while PPI users did have a higher dementia risk in unadjusted analyses, this association completely disappeared after accounting for other health conditions like diabetes and heart disease—which are themselves risk factors for dementia [1]. The authors concluded that the apparent link was due to 'confounding by indication,' meaning the people taking PPIs were already sicker and more prone to dementia for other reasons. A 2021 analysis of the FDA's adverse event database also found no signal linking PPIs to dementia, even with long-term use [6].
Why is the evidence so conflicting?
The main reason for the confusion is that it's very difficult to separate the effect of the drug from the effect of the reasons people take it. People who use PPIs long-term often have chronic health problems like obesity, diabetes, heart disease, and acid reflux—conditions that are themselves linked to a higher risk of dementia. When studies don't fully account for these factors, they can mistakenly attribute the dementia risk to the PPI [1]. This is called 'confounding.'
Another key factor is the difference between 'any use' and 'long-term, cumulative use.' Several studies found no increased risk with short-term or current PPI use, but did find a risk after many years of use. For example, the ARIC study found no increased risk for people currently taking PPIs, but a 33% higher risk for those who had used them for more than 4.4 years [2][10]. This suggests that if there is a real risk, it likely takes years of continuous use to appear. A 2024 genetic study (Mendelian randomization) also found no robust causal link, suggesting that the associations seen in observational studies may not be cause-and-effect [7].
So, should you stop taking your PPI?
The short answer is: not without talking to your doctor. The evidence is not strong enough to say that PPIs definitely cause dementia. A 2023 review of the topic concluded that 'a cause-effect relationship cannot at present be presumed' and that PPI use is best considered a 'marker' of future dementia risk, not a cause [8]. The same review and other experts advise that for people with a valid medical indication (like severe GERD, Barrett's esophagus, or to prevent stomach bleeding), the benefits of PPIs likely outweigh the potential risks [3][8].
However, because PPIs are often overprescribed and have been linked to other health issues (like vitamin B12 deficiency, kidney disease, and fractures) [3][5], it's wise to use them at the lowest effective dose for the shortest time needed. If you've been on a PPI for years without a clear reason, it's reasonable to ask your doctor if you can try stopping or reducing the dose. The guiding principle is to 'deprescribe' when possible [3][8]. The bottom line: don't panic, but do have an informed conversation with your healthcare provider about whether your PPI is still necessary.
About These Sources
This answer is built on 10 peer-reviewed studies — published from 2021 to 2026, 2 from 2024 or later, 7 in Q1 journals, collectively cited 190 times — selected as the most relevant from 11 studies that passed quality screening, drawn from 71 papers retrieved from a database of over 500 million.
Sources used in this answer
Signal and Noise: Proton Pump Inhibitors and the Risk of Dementia?
In a 22-year Canadian cohort study, high-dose PPI users had a higher dementia risk in unadjusted models, but after adjusting for medical conditions like diabetes and heart disease, the association disappeared, suggesting confounding explains the link.
Cumulative Use of Proton Pump Inhibitors and Risk of Dementia
In the ARIC study of 5,712 older adults, current PPI use was not linked to dementia, but those with >4.4 years of cumulative use had a 33% higher risk of developing dementia during follow-up.
Deprescribing proton pump inhibitors
This clinical review notes that while PPIs are associated with dementia in observational studies, no causality has been proven, and long-term use should be reserved for valid indications at the lowest effective dose.
Emulating a target trial of proton pump inhibitors and dementia risk using claims data
In a German claims analysis of 2.7 million people, PPI initiation was associated with a 54% higher risk of dementia (HR 1.54), and time-varying PPI use showed a 56% higher risk, suggesting a potential causal effect.
Association of Vitamin B12 deficiency with long-term PPIs use: A cohort study
This cohort study of 1,225 participants found that long-term PPI use was linked to a higher risk of vitamin B12 deficiency, especially in men aged 18-40, with omeprazole users showing lower B12 levels than pantoprazole users.
A pharmacovigilance study of association between proton pump inhibitor and dementia event based on FDA adverse event reporting system data
An analysis of the FDA adverse event database (2004-2020) found no significant signal linking PPI use to dementia events, even with long-term therapy of 3, 5, or 10 years.
Association between proton pump inhibitors and dementia risk: a Mendelian randomization study
A Mendelian randomization study using genetic data found no robust causal link between any PPI type and dementia after adjusting for multiple comparisons, suggesting observational associations may not be causal.
Proton Pump Inhibitors and the Risk of Dementia.
This review concludes that while chronic PPI use is associated with dementia in some studies, a cause-effect relationship cannot be presumed, and PPIs should be used at the lowest dose for the shortest duration needed.
Proton pump inhibitors and dementia: A nationwide population‐based study
In a nationwide Danish cohort of 1.98 million people, PPI ever-use was associated with a 36% higher dementia rate in those aged 60-69, with smaller increases in older age groups, and no association after age 90.
Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study.
This is a duplicate of paper 2, reporting the same ARIC study finding that >4.4 years of cumulative PPI use was associated with a 33% higher risk of incident dementia.