Link between indigestion drugs and dementia 'inconclusive'

“Indigestion pills taken by millions ‘could raise the risk of dementia by 50%’,” reports the Daily Mail.

This headline is about a class of prescription drugs known as proton pump inhibitors (PPIs), such as omeprazole. PPIs are widely used to treat heartburn (acid reflux), as well as stomach ulcers. They work by lowering acid production in the stomach.

The Mail’s headline sounds scary, but is no cause for alarm. The research behind the story provides no strong reason to stop taking PPIs as prescribed.

The study looked at the risk of being diagnosed with dementia within a seven-year window in German adults aged over 75. About 3,000 were taking prescription PPIs and 70,000 were not.

Those taking PPIs had a 44% higher risk of developing dementia compared with those not taking them – but it’s not accurate to say this was because of PPIs. The study couldn’t prove this, and there are many other plausible explanations.

For a start, the two groups weren’t very similar. Those taking PPIs had poorer health, and were more likely to be taking a greater number of medicines and have conditions linked to a higher risk of dementia.

A study where the characteristics of the two groups are more closely matched would be a useful next step.

It is not recommended that you suddenly stop taking PPIs, if you have been prescribed them, without first consulting your GP. Doing so could make your symptoms return suddenly.  

Where did the story come from?

The study was carried out by researchers from the German Center for Neurodegenerative Diseases and received no specific funding. 

It was published in the peer-reviewed medical journal JAMA Neurology.

The Mail and The Daily Telegraph’s reporting was accurate, although they did not delve into the limitations of the research in much detail.

Although, to be fair, both papers included some tempering statements towards the end of their articles – for example, that the study had found a link, but didn’t know how it might be caused biologically.

What kind of research was this?

This was a cohort study looking at a potential link between taking PPIs and developing dementia in older adults.

A cohort study measures changes over time and can highlight associations, such as using prescription PPIs and developing dementia later in life. The downsides of cohort studies are they cannot prove cause and effect, as they involve no randomisation or blinding.

People live their lives as they choose, and researchers measure and observe how this relates to the development of different conditions and diseases.

This means other factors, such as a person’s diet and lifestyle, can influence the specific link of interest – this is called bias and confounding.

There are different steps researchers can take to lessen this risk, such as adjusting for confounders in the analysis or closely matching the different groups, but it is difficult to eliminate this risk entirely. 

What did the research involve?

The study looked at the risk of being diagnosed with dementia within a seven-year window in German adults aged over 75. Of these, 2,950 (4.0%) were taking prescription PPIs, while 70,729 (96.0%) were not.

The data came from a large German health insurer, which held records of diagnosed diseases and prescribed drugs taken every four months over a seven-year period (2004-11). The study did not differentiate between dementia subtypes, such as Alzheimer’s disease or vascular dementia.

PPI use was defined as at least one PPI prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole per four-month period. This seems a sensible approach, as these are the most widely used PPIs.

The analysis took account of the following known confounders associated with dementia:

• age
• sex
• taking more than five medicines on top of PPIs
• having a pre-existing diagnosis of stroke, depression, heart disease or diabetes

The main analysis looked at the risk of being newly diagnosed with dementia in those taking PPIs, compared with those who did not take the drugs, over a seven-year period.  

What were the basic results?

At the study’s start, those taking PPIs were significantly different from those not taking PPIs in terms of age, sex, depression, stroke, heart disease, and taking more than five medicines on top of PPIs.

All these factors, as well as diabetes, were linked to a higher risk of dementia. The one interesting exception was heart disease diagnosis, which was linked to a lower risk.

Using PPIs was linked to a 66% increased risk of developing dementia compared with not using them (hazard ratio [HR] 1.66 95% confidence interval [CI] 1.57 to 1.76). This didn’t account for the confounding factors above. Once the analysis took these into account, the risk fell to 44% (HR 1.44, 95%; CI 1.36 to 1.52). 

How did the researchers interpret the results?

The researchers concluded that, ”The avoidance of PPI medication may prevent the development of dementia.

“This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice.

“Randomised, prospective clinical trials are needed to examine this connection in more detail.” 

Conclusion

This study found people taking PPIs had a 44% higher risk of developing dementia in a seven-year period compared with those not taking the drugs. However, it’s not accurate to say this was down to the PPIs – the study couldn’t prove this, and there are many possible explanations.

For a start, the groups weren’t very similar. Those taking PPIs had poorer health, and were more likely to be taking a number of medicines and have conditions linked to a higher risk of dementia, such as diabetes and heart disease.

After taking these factors into account in the analysis, the link between PPIs and dementia reduced from 66% to 44%.

It’s possible this adjustment wasn’t complete (residual confounding), or that many other factors not measured in this study could further explain the remaining risk increase (bias).

A study where the characteristics of the two groups are more closely matched would be a positive next step for this research area. 

The study also focused solely on PPIs, which are mainly prescribed for the protection and management of stomach ulcers. It does not apply to indigestion treatments like over-the-counter antacid treatments you might take for heartburn or indigestion, which work in a different way by neutralising excess stomach acid.

These limitations mean you should not stop taking prescribed PPIs. The link with dementia is uncertain, and is likely to be outweighed by the benefit of protecting the stomach against ulceration, bleeding and irritation.

If you want to reduce your risk of dementia and other serious health conditions, it’s recommended you:

• stick to a healthy diet
• maintain a healthy weight
• exercise regularly
• moderate your alcohol consumption
• stop smoking
• keep your blood pressure at a healthy level 

Links To The Headlines

Indigestion pills taken by millions ‘could raise the risk of dementia by 50%’. Daily Mail, February 16 2016

Indigestion drugs taken by millions linked to dementia. The Daily Telegraph, February 16 2016

Links To Science

Gomm W, van Holt K, et al. Association of Proton Pump Inhibitors With Risk of Dementia – A Pharmacoepidemiological Claims Data Analysis. JAMA Neurology. Published online February 15 2016