What did the “33% higher risk” study actually find?
The important point is that the headline is somewhat misleading if interpreted as “this medication causes dementia.”
A 2023 study published in Neurology examined 5,712 adults who were free of dementia at the relevant baseline assessment. Participants were followed for a median of about 5.5 years, during which 585 cases of dementia were identified.
Researchers found:
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People currently taking PPIs at the beginning of follow-up did not have a statistically significant increase in dementia risk: HR 1.1 (95% CI 0.9–1.3).
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People with more than 4.4 years of cumulative PPI use had an estimated 33% higher risk of developing dementia compared with people who had not used PPIs.
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The association was reported as HR 1.3, with a 95% confidence interval of 1.0–1.8.
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The researchers specifically stated that further studies are needed to determine whether there is a causal relationship.
So, “33% increased risk” means a relative increase in the observed risk—not that 33% of people taking the drug will develop dementia.
An important distinction
Suppose, purely as an illustration, that a particular group had a 10% baseline risk of dementia.
A 33% relative increase would correspond roughly to:
10% × 1.33 = 13.3%
That’s an increase of 3.3 percentage points, not an additional 33 percentage points.
The actual absolute risk for an individual depends on age, genetics, cardiovascular health, diabetes, blood pressure, lifestyle, and many other factors.
Which medicines are we talking about?
PPIs include drugs such as:
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Omeprazole — Prilosec and generic versions
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Esomeprazole — Nexium
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Lansoprazole — Prevacid
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Pantoprazole — Protonix
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Rabeprazole — AcipHex
They work by substantially reducing the production of stomach acid.
They’re different from simple antacids such as calcium carbonate, and they’re also different from H2 blockers such as famotidine.
Why might PPIs be associated with dementia?
Researchers don’t have a confirmed explanation.
Several possibilities have been proposed.
1. Vitamin B12
Long-term acid suppression can affect absorption of certain nutrients, including vitamin B12. Severe B12 deficiency can cause neurological problems, including memory and cognitive difficulties.
However, the 2023 study didn’t measure B12 levels, so the researchers could not establish that B12 deficiency explained their findings.
2. Effects involving amyloid
Another hypothesis involves amyloid, a protein involved in Alzheimer’s disease.
Researchers have proposed that PPIs could potentially affect enzymes involved in amyloid processing. This is a biological hypothesis, however—not proof that taking PPIs causes Alzheimer’s disease.
3. The underlying illness may be the real explanation
This is particularly important with observational studies.
People who take PPIs for many years may differ from people who don’t take them. For example, they may have more gastrointestinal disease, other chronic illnesses, different diets, or different medication patterns.
Those differences can potentially influence dementia risk independently of the PPI.
This is called confounding.
Does this prove that PPIs cause dementia?
No.
That’s probably the most important takeaway.
The study was observational. Researchers observed an association between long-term cumulative PPI exposure and dementia; they did not randomly assign people to take PPIs versus placebo for years.
The authors themselves concluded that future research is needed to establish the mechanism and determine whether the association is causal.
This distinction matters because observational studies can identify signals that deserve investigation, but they cannot by themselves establish that the medication caused the outcome.
What does broader research say?
The evidence isn’t simply “PPIs = dementia.”
A large umbrella review published subsequently examined 68 meta-analyses covering 11 categories of systemic medications. It found that much of the available evidence concerning medications and dementia is observational and can be affected by confounding and reverse causality. Its conclusions gave more consistent evidence of increased dementia risk for anticholinergic medications, while the evidence concerning PPIs is not sufficient to establish that they cause dementia.
That’s an important distinction because anticholinergic drugs are a different medication group. Some antidepressants, bladder medications, antiparkinson drugs, antipsychotics, and other medicines have anticholinergic properties.
For example, a very large JAMA Internal Medicine study involving 58,769 people with dementia and 225,574 controls found an association between high cumulative exposure to certain strong anticholinergic medications and dementia. But that study was also observational and therefore couldn’t establish causation.
Should someone stop omeprazole or another PPI?
Don’t stop a prescribed PPI solely because of this headline.
PPIs can be very useful—and sometimes important—for conditions such as severe GERD, ulcers, gastrointestinal bleeding prevention in selected patients, and certain other medical conditions.
Stopping long-term PPIs suddenly can also result in rebound acid production, causing symptoms to return or become substantially worse.
A better approach is to ask your doctor or pharmacist:
“Do I still need this PPI, and am I taking the lowest effective dose for the shortest appropriate duration?”
Depending on why you’re taking it, a clinician may consider continuing it, reducing the dose, changing the schedule, or trying another treatment.
If you’ve taken a PPI for years
It can be reasonable to have your medication list reviewed periodically, particularly if you’re older or taking multiple medications.
A clinician can consider:
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Why the PPI was originally prescribed
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Whether you still need it
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Your dose and duration
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Whether there is a documented indication for long-term treatment
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Other medications that may contribute to cognitive problems
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Vitamin B12 and other nutritional issues when clinically appropriate
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Whether reducing or discontinuing it is safe in your particular situation
The bottom line: the “33%” figure comes from an association seen among people with more than about 4.4 years of cumulative PPI exposure. It does not mean PPIs have been proven to cause dementia, and it does not mean that someone taking omeprazole every day has a 33% chance of developing dementia.
If you tell me the exact medication you take (for example, omeprazole 20 mg), your dose, and roughly how many years you’ve taken it, I can explain what the research means specifically for that medication and what questions to discuss with your doctor.