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12/14/2000

Protection Against Alzheimer's Disease Not Linked to NSAID Dose

Kate Traynor

A statistical link between avoidance of Alzheimer's disease and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is apparent at both low and high dosages, say Australian researchers.

In the November Archives of Neurology, the researchers reported that the use of aspirin and other NSAIDs was associated with a significant decrease in the prevalence of Alzheimer’s disease among elderly adults not residing in nursing homes. This relationship, the researchers reported, was noted for all NSAID dosages studied, even those at levels insufficient to suppress inflammation in the brain, bringing into question the mechanism of action for the drugs' effect.

These findings were based on data obtained from 536 adults, 75 years and older, who underwent medical and neurological assessments as part of the Sydney Older Persons Study. The study participants lived in noninstitutional settings in Sydney, Australia, and were recruited for the study between August 1991 and March 1994.

Using information from medical evaluations, the researchers divided the study participants into four groups. Seventy-eight enrollees were classified as having Alzheimer’s disease without evidence of vascular dementia, 45 had vascular dementia with or without Alzheimer’s disease, and 40 had other forms of dementia. The remaining 373 participants, who had no signs of dementia, were used as a control group.

The research team looked for statistical differences in drug use among the dementia and control groups. Initial analyses focused on five drug classes: aspirin, NSAIDs, and corticosteroids, all known to have anti-inflammatory effects; histamine H2-receptor antagonists, often taken in the early 1990s to protect the gastrointestinal tract against the damaging effects of the preceding anti-inflammatory drugs; and acetaminophen, whose use was expected to be the same by all study groups. The research team also looked for other drugs whose usage patterns differed among adults in the dementia and control groups.

People with Alzheimer’s disease—but not other forms of dementia—were significantly less likely than adults without the disorder to have used aspirin, NSAIDs, antirheumatics other than NSAIDs, or angiotensin-converting-enzyme inhibitors, the researchers found. Adults with vascular dementia, with or without Alzheimer’s disease, were more likely than participants in the other groups to have used diuretics.

The researchers also examined whether the amounts of aspirin and other NSAIDs used by the participants differed among the four study groups. Dosage ranges designated as "low" were those unlikely to deliver sufficient drug to suppress inflammation in the brain.

Aspirin dosages of less than 175 mg/day were classified as low, as were NSAID dosages equivalent to naproxen 500 mg/day or less. NSAID dosages exceeding the equivalent of naproxen 1,000 mg/day were considered high. Aspirin dosages of 175 mg/day or more were classified as medium. One person in the control group consumed 1,200 mg/day of aspirin, but all other aspirin users in the medium-dose group took 175 to 650 mg of the drug per day.

According to the research team’s analysis, all NSAID dosages were associated with similar decreases in the prevalence of Alzheimer's disease. Thus, the researchers proposed that the purported link between NSAID use and protection against Alzheimer’s disease involves an undetermined mechanism unrelated to anti-inflammatory effects.