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Do NSAIDs Have a Protective Effect in Alzheimer's Disease?

Am Fam Physician. 2002 Apr 1;65(7):1446.

A possible inflammatory mechanism for Alzheimer's disease has long been postulated given the evidence of chronic inflammatory changes in brain specimens of affected patients. A number of retrospective studies in the early 1990s reported on a possible protective effect of anti-inflammatory treatments, especially using nonsteroidal anti-inflammatory drugs (NSAIDs), against the development of Alzheimer's disease. Initial enthusiasm faded, however, when observational studies produced conflicting results. In ‘tVeld and colleagues examined data from an expanded interval (eight years) that prospectively tracked NSAID use and the development of Alzheimer's disease and vascular dementia.

Using a nationwide pharmacy database in the Netherlands (rather than error-prone recall by study subjects), the investigators tabulated the use of NSAIDs in a group of 7,983 persons older than 55 years who were participating in a population-based aging project. Excluding patients who already had evidence of dementia at the study onset, the investigators screened the 6,989 participants for dementia approximately three and eight years later.

Among study participants, the most commonly used NSAIDs were diclofenac, ibupro-fen, and naproxen, which accounted for 83 percent of NSAID prescriptions. In persons whose cumulative use of NSAIDs totaled less than one month during the study, the risk for developing Alzheimer's disease was not significantly different from the risk in persons without NSAID use. The relative risk of Alzheimer's disease dropped by 17 percent when cumulative use was between one and 23 months, and decreased by 80 percent when total NSAID use was greater than 24 months. Use of aspirin alone did not afford the increasing protection with prolonged use that was seen with other NSAIDs. Only Alzheimer's dementia was less common in persons with prolonged NSAID use; the incidence of vascular dementia was unchanged. An accompanying editorial suggests that the positive results of this longer-term study may differ from the inconclusive results of shorter studies of NSAID use because of a need to interrupt the inflammatory changes of Alzheimer's disease a number of years before any initial signs of dementia appear.

The authors conclude that prolonged NSAID use has a beneficial effect on the risk of developing Alzheimer's disease.

BILL ZEPF, M.D.

In‘tVeld BA, et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med. November 22, 2001;345:1515–21, and Breitner JC, Zandi PP. Do nonsteroidal anti-inflammatory drugs reduce the risk of Alzheimer's disease? [Editorial] N Engl J Med November 22, 2001;345:1567–8.


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