February 15, 2016

expert reaction to study investigating proton pump inhibitors (PPIs) and risk of dementia

A study published in JAMA Neurology has reported that patients who used a specific type of drug (proton pump inhibitors) for the treatment of gastrointestinal diseases had an increased risk of dementia.

Dr Tara Spires-Jones, Reader and Chancellor’s Fellow, Centre for Cognitive and Neural Systems, University of Edinburgh, said:

“This study looked at the medical records of a large group of people over 75 years of age and found that people taking proton pump inhibitors (PPIs) had a higher likelihood of developing dementia. PPI drugs are used to treat ulcers and gastroesophageal reflux (heartburn).

“This is a large study showing a possible link between the use of PPI drugs and developing dementia; however, it is important to keep in mind that this type of study has limitations and does not show that these drugs necessarily cause dementia. The increased odds of having dementia after taking these drugs may be directly related to the proton pump inhibitors, or it may be due to something else associated with PPI use. For example, the use of PPI is higher amongst obese people and may be higher in people who smoke – and obesity and smoking are risk factors for dementia.  Further research is necessary to determine whether PPIs actually contribute to developing dementia.”

Prof. Martin Rossor, Professor of Clinical Neurology, UCL, said:

“Many medicines that are used for one particular disease are found to have an effect to either worsen or improve a different disease. Before assuming that proton pump inhibitors do increase the risk of dementia more studies will be needed to ensure that other factors that may lead to the use of PPIs such as smoking are not the primary cause of the increased risk. The observation raises many questions for future research and importantly emphasises the importance of considering the effects on cognition of commonly prescribed drugs.”

Prof. Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“These findings should be treated with considerable caution.  Firstly it is clear that the PPI users and non-users differed a great deal in factors potentially associated with increased dementia. The key differences are shown cleary in Table 1.

“It is also shown in Table 2 that most of these factors were associated with an increased risk of incident dementia. This has two major consequences. Firstly that any measurement error or imprecision in these measured confounding factors would mean that adjustment for them was incomplete so the effects reported could well be exaggerated.

“Secondly, as the authors note, there is considerable scope for further, unmeasured, factors to differ between users and non-users, and hence not taken into consideration and may be at least a partial explanation of the findings with PPIs.

“There does not seem to be any differential access to health care in users and non-users, so diagnoses will not necessarily be more likely in the users. There is a possibility that the users of PPIs lived longer and could have been more likely to have had the chance of a diagnosis of dementia. This may or may not be the case (what is called a competing risk) but does not seem to have been considered.

“Although early (in 2004) diagnoses were excluded, the subsequent period from 2005 to 2011 is quite short for an effect and the graph shows that the association appears very soon after starting follow-up.

“The absolute risks are not made very clear. The effects may not be caused by the proton pump inhibitors or if they are they may be exaggerated.

“The data from this paper should not be interpreted as suggesting that people cease their proton-pump inhibitor treatment because of this report.”

Dr James Pickett, Head for Research at Alzheimer’s Society, said:

“A growing body of evidence now suggests that some medications may be linked to slightly increased risk of dementia. This research adds to that list proton pump inhibitors, which are a very common type of medicine taken by older people for heartburn or peptic ulcers. However, heavy users of this medication tend to be in poorer health anyway, with a higher risk of having diabetes and heart disease – both of which are risk factors for dementia. It is, therefore, very difficult to look at these risk factors based on health records alone and determine how they influence the risk of dementia.

“Further research is needed to tease apart the cause and effect of this medication and dementia. While some medications may have a small part to play in the development of dementia, there is a lot a person can do to reduce their risk of developing the condition, such as following a balanced diet, exercising regularly and managing vascular risk factors such as blood pressure and diabetes.”

Dr Elizabeth Coulthard, Consultant Senior Lecturer in Dementia Neurology, University of Bristol, said:

“It is important to identify risks for dementia in order to try and eliminate them. This study may point to an association between proton pump inhibitor use and dementia. However, the paper does not tell us that using a proton pump inhibitor causes dementia.  Although the study involves large numbers of people, the design has several limitations. Two groups of people are investigated: one taking and one not taking proton pump inhibitors. These two groups are not well matched for other factors that could contribute to dementia, making it difficult to draw firm conclusions from the comparison. In addition, one important factor that is associated with both proton pump inhibitor use and dementia is body weight and body weight is not recorded in this study.

“Treatment of gastric ulcers has been transformed by the use of proton pump inhibitors reducing the risk of potentially fatal bleeding and the need for major surgery. While this study may act as justification for a larger better controlled trial of the benefits and risks of proton pump inhibitors, the evidence is not strong enough to suggest people should stop taking proton pump inhibitors.”

‘Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis’ by Willy Gomm et al. published in JAMA Neurology on Monday 15 February 2016.

Declared interests

Dr Tara Spires-Jones: “I have no relevant conflicts of interest.”

Prof. Martin Rossor: “No relevant interests.”

Prof. Stephen Evans: “I have no interests to declare in relation to this issue.”

Dr James Pickett: No interests to declare.

Dr Elizabeth Coulthard: “I have no conflicts.”