Last Updated: 2008-05-13 13:46:57 -0400 (Reuters Health)

NEW YORK (Reuters Health) – Long-term use of naproxen or celecoxib did not prevent cognitive decline in a primary prevention trial of more than 2000 elderly individuals with a family history of Alzheimer’s disease, according to a May 12 online publication by the Archives of Neurology.

Indications from observational studies that nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer’s disease (AD) support the theoretical role of cytokine-mediated inflammatory processes in neurodegenerative disorders, Dr. Barbara K. Martin, at Johns Hopkins Center for Clinical Trials in Baltimore, and her associates note.

The Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT), sponsored by the National Institute on Aging, included 2117 cognitively intact men and women age 70 and older with at least one first-degree relative with AD-like dementia.

Subjects were randomly assigned to celecoxib 200 mg twice daily (n = 617), naproxen sodium 220 mg twice daily (n = 596), or placebo (n = 904).

Initiated in March 2001, ADAPT was terminated in December 2004, after celecoxib was linked to increased cardiovascular risk in another trial.

"The ADAPT cognitive function results through 6 months after study treatment cessation do not show a protective effect with the use of NSAIDs and may suggest that cognitive scores are lower," the researchers report.

Scores on the Modified Mini-Mental State Examination were lower over time for both groups compared with placebo, and a global summary score from seven individual cognitive tests were significantly lower over time for naproxen but not for celecoxib.

However, the mean differences by treatment group are small, Dr. Martin’s group points out, and their clinical significance is unclear.

It is possible, they suggest, that different NSAIDs may offer more benefit, or that earlier treatment initiation, before the development of any subclinical neuropathology, may be necessary for a protective effect to be realized.

"For now," the investigators recommend, "naproxen and celecoxib should not be used for the prevention of AD."

Arch Neurol 2008;65.

Copyright Reuters 2008. Click for Restrictions