Elderly African Americans who are chronic users of acidinhibiting medications in the family that includes Zantac, Pepcid and Tagamet have 2 1/2 times the normal risk of developing dementia, Indiana researchers reported Friday.
The drugs block production of stomach acid by inhibiting so-called histamine-2 receptors; a pump in the stomach releases hydrochloric acid when stimulated by histamines.
But they also inhibit the brain's cholinergic system, which is involved in memory and cognition. Low levels of cholinergic activity have previously been linked to dementia.
There have been hints that the drugs, known as histamine-2 receptor antagonists, might be linked to dementia, but previous studies have come down on both sides of the question, said Dr. John Morris of Washington University in St. Louis, who was not involved in the study.
"This is certainly not the final word on the potential risk of these drugs," he said. "But what it tells us is that, for older adults, drug use should be considered very carefully."
Dr. Constantine G. Lyketsos, a psychiatrist at Johns Hopkins University, who was also not involved in the study, said: "This is one of the medicines we worry about when people with Alzheimer's are taking them. It can make memory worse and lead to confusion. Whether they will make it more likely that someone will develop Alzheimer's or dementia is still an open question."
GlaxoSmithKline, which manufactures Tagamet and Zantac, did not return calls seeking comment.
The study did not look at other races, and there was not enough data to suggest a risk from a different family of acidinhibiting drugs called proton pump inhibitors, which includes Prilosec, Nexium and Prevacid.
The histamine-2 receptor antagonists are among the most commonly prescribed medications in the United States, with more than 16 million prescriptions dispensed in 2005 in addition to over-the-counter sales. They are used to treat ulcers, acid reflux and other gastrointestinal disorders.
The study, published in the Journal of the American Geriatrics Society, was conducted by Dr. Malaz Boustani, a geriatrician at the Indiana University School of Medicine. He said he noticed that a significant number of his hospitalized patients appeared confused when they were taking medications to reduce acid reflux.
To explore the link, he looked at 1,558 black Indianapolis residents who had taken part in other studies through the school. None had dementia when the study began.
Each member was surveyed for use of the histamine antagonists and other drugs at the beginning of the study, at the end of three years and at the end of five years. The team also physically checked their medications.
The researchers found that, when they controlled for possible confounding factors, those taking the drugs were 2.42 times more likely to have dementia, which is marked by confused thinking, poor memory and impaired reasoning powers.
Boustani said he was not yet prepared to suggest that people stop taking the drugs. The proton pump inhibitors, he noted, are associated with an increased risk of osteoporosis, so that "if you switch, you then might deal with other alternatives.
"This is a very limited study in a specific population, but it picked up a signal that really needs to be confirmed," Boustani said. "The picture is really not clear yet."