Guest post by Dr. Susan Molchan, a psychiatrist with extensive experience in clinical research at the National Institutes of Health. She is the former program director for clinical dementia research at the National Institute on Aging. And she is one of our most active contributors.
….based on an observational study by German researchers and published in JAMA Neurology. The journal manuscript is entitled, “Association of Proton Pump Inhibitors with Risk of Dementia.” (italics mine)
To report the findings accurately, journalists need to watch their language. An association does not indicate that the drugs cause or increase the risk of dementia. This could only be shown by a true experiment, a randomized controlled trial, where one group of people is put on PPIs for a long time and one on a placebo. Many journalists noted this in their articles. A randomized controlled trial is not likely to be done in this case though, and editorial commentator and epidemiologist Dr. Lewis Kuller from the University of Pittsburgh noted that further studies can look at people who are diagnosed with dementia compared to those without dementia where there is a good history or PPI use (case-control studies), and can see if PPI use is associated with pathological changes in the brain.
The researchers themselves overstate their findings, in my opinion, saying in their abstract that those patients taking PPIs “had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication…The avoidance of PPI medication may prevent the development of dementia.”
The researchers examined an insurance claims database that included over 73,000 people, 75 and older, and free of dementia at the beginning of the study. They found that over 7 years those who took PPIs had a 44% increased probability of receiving a diagnosis of dementia (reported as a hazard ration of 1.44)
As Dr. Kuller points out, the German researchers found a similar association in another long term study of primary care patients, and this enhances the validity of their finding. Dr. Kuller points out reasons the drugs could cause an increase in dementia: they cross the blood-brain barrier, they can lower vitamin B12 levels, which, if too low, causes dementia, and in animal studies PPIs interact with amyloid and tau, proteins that muddle the brain in Alzheimer’s disease. He also notes why PPIs may not be causal: older people take many drugs, and these drugs are taken for a number of conditions. He notes that polypharmacy, taking many drugs, was also noted to be a risk factor for dementia in both German studies. People who take lots of drugs for several medical conditions (that may themselves increase dementia risk) go to the doctor more, hence may tend to be diagnosed with dementia more.
(Publisher’s note: It always befuddles me why journalists wouldn’t take advantage of the freebie 2nd opinion that journal editorials provide them. Why wouldn’t you read Kuller’s editorial for another perspective on the work you’re reporting on? Why would you go with a single-source story – practicing the stenography of regurgitating what was reported by the researchers – and NOT at least nod in the direction of the accompanying editorial? Fortune did. Forbes did. MedPageToday did. NPR did, but didn’t cite the questions we captured, above. Others didn’t acknowledge the editorial at all. )
Since PPIs debuted over 25 years ago, the Food and Drug Administration (FDA) has noted that the drugs are associated with increased risk of fractures in the hip, wrist, and spine; lower magnesium, calcium; and infection with Clostridium difficile, a form of severe diarrheal infection that can be life-threatening especially in older people.
Millions of people take these drugs for symptoms of acid reflux or heartburn, or gastro-esophageal reflux disease, a mouthful and marketing triumph popularly known as GERD. Many who take them do not need them. A study from the Johns Hopkins School of Medicine for example showed that over 60% of PPIs prescribed in an inpatient setting were not for an FDA approved or clinically indicated condition, and many of these prescriptions were continued once patients went home.
In the U.S., drugs that people will take long-term are heavily marketed to both doctors and patients. We don’t know anything about a drug’s long-term effects when it is initially approved. Careful observational such as that reported are important to fill out this information. Although it still wouldn’t be definitive, If future studies can show that people taking higher compared to lower doses or for longer versus shorter time periods have higher probabilities of dementia, this would add substantially to the “causal” side of the evidence stack.
Journalists, medical journal editors, and scientists themselves can help people better understand studies and the risks of the drugs they take if they would take a little more care to watch their language. We have a primer that can help with suggestions for accurate language to use to describe the difference between correlation and causation.
(Also see the analysis by the NHS Choices Behind the Headlines site, “Link between indigestion drugs and dementia ‘inconclusive’ “)