Extended use of nonsteroidal anti- inflammatory drugs (NSAIDs), such as ibuprofen, may reduce the risk of developing Alzheimer disease by as much as 80%, according to a seven-year prospective study published on 22 November in the New England Journal of Medicine (NEJM). If these results are confirmed in prevention trials, the drugs could have an enormous public health impact, say experts.

"Given the global spread of this disease, with about 11 million sufferers of Alzheimer dementia worldwide," says WHO mental health expert Dr José Bertolote, "any evidence such as this clearly has the potential to be of public health significance. We have to be hopeful, however, that these early findings will live up to the expectations they raise."

The new study, conducted by researchers at Erasmus University Medical School in Rotterdam, the Netherlands, followed nearly 7000 people over an average of just under seven years. All subjects were aged 55 or older and free of dementia at the beginning of the study. The researchers evaluated the mental and neurological health of the participants at the beginning, middle and end of the study. Throughout the study, the researchers used computerized pharmacy records to keep track of the subjects' NSAID use. (NSAIDs were available only by prescription in the Netherlands during most of the study.)

Analysis revealed that study participants who used NSAIDs for two or more years were 80% less likely to develop Alzheimer disease compared to people who didn't use the drugs. Ibuprofen, naproxen, and diclofenac were the most popular NSAIDs, together accounting for about 83% of the total number of NSAIDs taken by participants in the study.

This isn't the first study to find a link between NSAIDs and Alzheimer risk. "There have been at least 20 epidemiological studies looking at NSAIDs and Alzheimer disease," Dr Peter P. Zandi of Johns Hopkins University in Baltimore, Maryland, USA, told the Bulletin. But this latest study is especially strong because it was prospective, involved a large population group, included a long follow-up period, and gathered data from pharmacy records rather than relying on the subjects' memory of past NSAID use, Zandi and his colleague at Johns Hopkins, Dr John Breitner, wrote in an accompanying editorial in the NEJM.

It is unclear how NSAIDs might decrease Alzheimer risk. Inflammation is believed to be involved in Alzheimer. For this reason, "we think that inhibition of inflammation [by these drugs] may play a role", Dr Bruno Stricker, senior author of the study, told the Bulletin. But that is only one hypothesis. A study recently published in the 8 November issue of Nature suggested that NSAIDs might lessen Alzheimer risk by reducing brain levels of amyloid-ß, a protein that accumulates in the brains of people with the disease. The exact mechanism by which these drugs might achieve this result is not entirely clear, but blockage of an enzyme involved in the production of amyloid-ß is one possibility.

For now, the ability of NSAIDs to prevent Alzheimer disease awaits verification from clinical trials under way. "Widespread use [of NSAIDs for this purpose] should be discouraged until prospective double-blind randomized trials have confirmed this and have assessed the ideal dose and benefit/risk ratio," Stricker told the Bulletin.

But if the benefits of NSAIDs are validated in further trials, the public health gains would be huge. "If a particular drug can be proven to prevent Alzheimer disease, it would have a tremendous public health impact," Dr Neil Buckholtz, Chief of the Dementias of Aging Branch of the National Institute on Aging in Bethesda, Maryland, USA, told the Bulletin. "People have estimated that if you delayed the onset of Alzheimer by five years, you would decrease the number of people with the disease by half and cut the cost too."

Those numbers could quickly add up. WHO estimates that by the year 2025 more than 22 million people worldwide will have Alzheimer disease.

Christie Aschwanden, Nederland, Colorado, USA