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DG DISPATCH - ISSSAT: Some Drugs May Protect Against Alzheimer's, Others Might Increase Risk By Cameron Johnston Special to DG News STOCKHOLM, SWEDEN -- April 12, 2000 -- Many observational studies conducted in the past have pointed to an association between a reduced risk of Alzheimer's disease and the patient's past history of using nonsteroidal anti-inflammatory drugs (NSAIDs). Now, to that list, we might also add H2 receptor antagonists (H2RAs) and perhaps even vitamins C and E. At the same time, omeprazole, a drug used in the treatment of gastric ulcers, has been associated with an increase in the relative risk for developing Alzheimer's disease. In a presentation at the 6th International Stockholm-Springfield Symposium on Alzheimer Therapy (ISSSAT), John Breitner, MD, of the Johns Hopkins University School of Public Health, in Baltimore, MD, discussed the results of a study looking at the use of these drugs among a population of elderly people. He concluded that there must be something present in antioxidants and H2RAs that offers some form of limited protective effect against Alzheimer's for these people. Dr. Breitner's study looked at 5,092 people over the age of 65 living in one county in the state of Utah. Out of that population -- which comprised around 90 per cent of the county's total residents, there were 335 cases of dementia, of which 201 were confirmed to be of the Alzheimer's type. The Alzheimer's cases were matched with a group of more than 400 controls and then their drug use habits were compared -- by checking medicine cabinets to see what drugs the people were using, and drawing a correlation between drug use and the risk of developing the disease. Using mathematical analyses, it was determined that those patients who used NSAIDs regularly had a 0.43 odds ratio of developing the disease; those who used aspirin had a 0.50 odds ratio; and those who used aspirin and NSAIDs in combination had a 0.17 odds ratio. By comparison, Dr. Breitner said there was "almost no odds ratio for subjects who used acetaminophen." Similarly, the prevalence was reduced among users of H2RAs (odds ratio=0.42) and of other antacids (odds ratio=0.63). However, those subjects who used the proton pump inhibitor, omeprazole, actually showed a 1.46 odds ratio, meaning they were at signifcantly greater risk of developing Alzheimer's than those who did not use that particular drug. The findings were all statistically significant -- in the case of NSAIDs they were highly statistically significant -- but some of the data was "heavily confounded" by the use of multiple antacids, including over-the-counter varieties, Dr. Breitner said. "To the extent that these data can show you anything, the results are highly consistent with our hypothesis," he said. While there was an inverse correlation between the levels of vitamins C and E that people consumed and the odds ratio for developing Alzheimer's, Dr. Breitner said that, in his opinion, the amount of additional C and E that people receive from multi-vitamins is not sufficient to confer this beneficial effect, and therefore, warding off Alzheimer's with the help of vitamins must depend on vitamin-rich diets. Furthermore, it appears that those who consume vitamin E but not C have less risk than those who consume C but not E. Meanwhile, those who consume both have a statistically significant 0.32 odds ratio for developing the disease. Dr. Breitner speculated that this benefit stems from the fact that NSAIDs block the release of the inflammatory cyclooxygenase-2 (COX-2). That COX-2 mediates the oxidation of arachidonic acid which is just one part of a long cascade by which multiple inflammatory processes extend deep into the brain and affect the very substrate that is responsible for learning and for long- and short-term memory. He is now undertaking a major trial in which more than 2,600 people over the age of 70 who have a first degree relative with Alzheimer's-like dementia will be randomized to receive either placebo, the COX-2 inhibitor, celecoxib, or naproxen. This will be one of the first prospective double-blind, randomly controlled trials to assess the use of anti-inflammatory drugs as a potential preventive for Alzheimer's disease. E-mail this page to a friend or colleague! To print, use this version