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New Research Shows Link Between PPI Heartburn Drugs and Dementia Risk

Feb 17, 2016

A research study published online on February 15, 2016 in JAMA Neurology reports an increased risk for dementia in elderly German patients who repeatedly used certain drugs for gastric reflux or peptic ulcers.

The class of drugs—proton pump inhibitors (PPIs)—is a widely prescribed class of medications and includes Prevacid (lansoprazole), manufactured by Novartis, and Nexium (esomeprazole) and Prilosec (omeprazole), both made by AstraZeneca, Reuters Health reports.

Britta Haenisch of the German Center for Neurodegenerative Diseases in Bonn, senior author, says the study can provide only a statistical association between PPI prescriptions and dementia in the elderly, but it cannot prove that PPIs cause dementia, Reuters Health reports. "To evaluate cause and effect relationships between long-term PPI use and possible effects on cognition in the elderly randomized, prospective clinical trials are needed," Haenisch said.

Haenisch told Reuters Health in an email that the researchers "focused on long-term regular PPI prescription for at least 18 months." They reviewed medical records for more than 73,000 patients age 75 and older, most of them women, from 2004 through 2011. Twenty-nine hundred fifty patients were classified as regular PPI users, meaning they had at least one prescription for one of the drugs every four or five months over an 18-month period. PPIs are also available over-the-counter in nonprescription strength but the researchers looked only at prescription PPIs.

During the years covered by the study, 29,510 people developed dementia. Regular PPI users were 44 percent more likely to develop dementia than those who were not taking PPIs, according to Reuters Health. Haenisch said the researchers could not know whether some of the study subjects were already at increased risk for dementia.

In an editorial accompanying the study results, Dr. Lewis H. Kuller of the University of Pittsburgh noted that PPI use and dementia may both be influenced by similar risk factors. For example, Kuller wrote, in the Women's Health Initiative, women who took PPIs were more often obese, had arthritis, and were generally in poorer health than other women, and these factors may increase dementia risk. Use of PPIs is known to carry other health risks, including increased risk of kidney disease and bone fractures, low magnesium levels, gastrointestinal infections, Clostridium difficile infection and pneumonia, Reuters Health reports.

Haenisch explains that PPIs work by reducing gastric acid production, but the "underlying mechanism by which PPIs might influence cognition is yet to be determined." Some of the drugs may cross the blood-brain barrier and interact with brain enzymes, or they may be associated with vitamin B12 deficiency, which may promote neurological damage, according to Haenisch. PPIs appear to effect levels of amyloid beta and tau, proteins associated with Alzheimer's disease, CBS News reports.

Haenisch said overprescribing of PPIs has been reported. One study found that up to 70 percent of PPI prescriptions were inappropriate for the patient, Reuters Health reports. In January, JAMA Internal Medicine published a study reporting that 25 percent of long-term PPI users could stop taking the medication without suffering increased heartburn or acid reflux, according to CBS News.

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