Oct. 9, 2003 -- The race is on to develop drugs to slow the progression of Alzheimer's disease, with dozens of new treatments under investigation. Now, intriguing early research suggests that cheap and effective Alzheimer's drugs may already be sitting in your medicine cabinet.
Canadian researchers will report this week that two common antibiotics, taken together, can change the course of Alzheimer's disease and that these changes seem to be long lasting. The findings are to be presented in San Diego at the 41st Annual Meeting of the Infectious Disease Society of America.
Though the findings must be confirmed, lead investigator Mark B. Loeb, MD, of Ontario's McMaster University, says antibiotics may have a role in the treatment of patients who are not responding to other therapies. He warned, however, that long-term use of antibiotics is probably not a good idea, due to the possibility of developing antibiotic resistance.
Antibiotics vs. Placebo
Roughly 4 million people in the U.S. are believed to have Alzheimer's disease, and that number is expected to more than triple within the next four decades as our society continues to age.
So far, the only drugs approved by the U.S. Food and Drug Administration to treat the disease are Reminyl and other agents in the class known as cholinesterase inhibitors. These drugs help preserve brain chemicals linked to memory but do not directly slow brain degeneration.
Loeb tells WebMD that his research team began studying antibiotics in Alzheimer's disease after a 1998 study found an increased incidence of the infection Chlamydia pneumoniae in the brains of deceased Alzheimer's patients.
In the newly reported study, 101 patients with mild to moderate Alzheimer's disease at five medical centers throughout Canada were treated with either a three-month course of the antibiotics doxycycline and rifampin or inactive placebo pills. Neither the study investigators, the treating physicians, nor the patients knew who got which treatment.
Standardized tests measuring brain function were administered at the start of the study and three months after the patients were taken off the treatments. At the follow-up evaluation, mental scores among the patients in the placebo group had declined by an average of 2.75 points more (on a 70-point scale) than the patients who took the antibiotics. Though the differences in the scores were not considered to be much different from those taking placebo, it still indicated that the patients who took the antibiotics had slower mental decline.
"The slowing in mental decline that we saw was in the same ballpark as that seen with the cholinestrase inhibitors," Loeb tells WebMD. "Because of this, I think it might be prudent to consider an antibiotic regimen for patients who are doing badly on [cholinesterase inhibitors]."
Why Antibiotics Might Work
Loeb and his research team did not find any evidence of an increased incidence of Chlamydia pneumoniae infection among the patients enrolled in his study. He says he now believes that antibiotics may slow dementia not by killing infection, but by interfering with the accumulation of protein plaques in the brain believed to cause Alzheimer's disease.
In early animal studies, Harvard University researcher Ashley Bush, MD, PhD, found that an antibiotic abandoned since the 1970s dissolved these so-called beta-amyloid plaques by stripping them of the copper and zinc that helps bind the plaques together.
Amazingly, this drug, known as clioquinol, actually eliminated plaques in a third of the animals, suggesting that it could potentially reverse as well as prevent mental decline, Bush says.
Bush tells WebMD that human studies stemming from this animal research have proved "very promising" and are scheduled for publication by the end of the year.
"It is a total coincidence that this is an antibiotic," he says. "It's effectiveness has nothing to do with the fact that it kills organisms, and everything to do with the fact that it keeps plaques from forming by pulling the excess copper and zinc out of them."
Alzheimer's Group Expresses Caution
In response to the research by Loeb and colleagues, the Alzheimer's Association issued a statement expressing caution about the findings because of the study's small sample size. The group called for larger, well-controlled clinical trials to confirm the study's conclusions.
A spokesman for the Alzheimer's Association called the findings "provocative" but added that the small number of patients precludes generalization to larger populations with Alzheimer's disease.
Samuel Grandy, MD, PhD, who is vice chairman of the group's Medical and Scientific Advisory Counsel, tells WebMD he also has concerns about acquired antibiotic resistance.
"Obviously, antibiotic resistance can be very serious in an elderly population," he says. "That is one reason why further study is so important. We have to confirm that this therapy works, and that its benefits outweigh the risks."