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Long-term NSAID use tied to reduced risk of Alzheimer's disease

WESTPORT, CT (Reuters Health) – The risk of Alzheimer's disease is significantly reduced in subjects who use nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 2 years, according to results of a prospective study reported in The New England Journal of Medicine for November 22.

At baseline between 1990 and 1993, a total of 6989 subjects at least 55 years old were enrolled and deemed to be free of dementia. Dr. Bas A. in 't Veld, of Erasmus Medical Center in Rotterdam, and colleagues followed the subjects until they died or were diagnosed with dementia, or until the end of 1998.

During average follow-up of 6.8 years, 293 subjects were diagnosed with Alzheimer's disease, 56 were diagnosed with vascular dementia, and 45 were diagnosed with other types of dementia.

Information regarding the use of NSAIDs was obtained from computerized pharmacy records. Approximately 83% of the prescriptions for NSAIDs were diclofenac, ibuprofen, or naproxen.

The risk of Alzheimer's disease was 0.95 for subjects who had used NSAIDs for 1 month or less compared with those who had not used NSAIDs. The risk was 0.83 for those who had used such drugs for more than 1 month but less than 24 months, and 0.20 for those who had used NSAIDs for a cumulative period of 24 months or more. The effect on risk was unrelated to the number of doses used per day or the subject's age at baseline.

In contrast, Dr. in 't Veld and his associates observed, use of NSAIDs was not linked to a reduced risk of vascular dementia. Use of oral salicylates was associated with an increased risk of vascular dementia, with nearly a five-fold increase in risk for those who used them for more than 2 years compared with those who did not use salicylates at all.

In an editorial, Dr. John C. S. Breitner and Dr. Peter P. Zandi of Johns Hopkins University in Baltimore point out that the data show that the protective effect of NSAIDs extends until approximately 2 years before dementia diagnosis.

"A two-year lag between exposure and effect explains all the negative findings from prior studies because–with the notable exception of the Baltimore study–all such analyses relied on relatively brief periods of follow-up after participants were classified according to their use of NSAIDs," the Johns Hopkins researchers suggest.

N Engl J Med 2001;345:1515-1521.

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