Can NSAIDs prevent Alzheimer's Disease?

Alzheimer's disease (AD) gums up the brainworks with tangled neurons and protein plaques. Much of the damage occurs, however, as a result of an inflammatory response to these changes. Scientists theorized that the regular use of anti-inflammatory drugs such as Advil, naproxen, or Celebrex (also known as non-steroidal inflammatory drugs or NSAIDs) could slow down or prevent this degenerative disease.

The Alzheimer's Disease Anti-inflammatory Prevention Trial(1) enrolled over 2,000 seniors aged 70 years and older and followed them through 7 years of life correlating the use of NSAIDs (naproxen 220 mg. twice daily, Celebrex 200 mg. twice daily, or a look-alike placebo with no anti-inflammatory properties at all). All participants had a family history of AD and were thus considered to be at increased risk for developing the disease.

Made no difference what the septuagenerarian subjects took--naproxen, Celebrex, or no drug at all--with respect to their subsequent tendency to drift towards dementia. In fact, there was 'weak evidence' for a detrimental effect of naproxen.

The problem, however, is that this really wasn't a preventive trial at all. By the time old folks enter their eighth decade, they may well already be on the road to AD. Chemopreventive studies--i.e. those research trials seeking substances that actually protect against the development of AD through a neuroprotective substance-- would need to be undertaken on younger subjects over a longer period of study, an approach that is prohibitively expensive. The studies that suggest that NSAIDs are indeed useful in AD prevention are largely observational and/or retrospective; large populations are quizzed as to their health habits and medication usage, and these reports are correlated with present or future health outcomes. And if you've ever quizzed an old person about their drug use now and in the past, you may well wonder as do I how accurate those self-reports really are.

While the jury's still out as to whether NSAIDs are useful against AD, there is evidence that they may lower the incidence of cancer, and they certainly are good for pain. On the other hand, a recent study(2) showed a strong link between their use in patients also on anti-depressants such as Prozac or Lexapro (aka SSRIs) and gastrointestinal bleeding. Those on this pharmaceutical duet were 4.8 times more likely to bleed from their upper GI tract.
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1. ADAPT Research Group. Cognitive Function Over Time in the ADAPT: Results of a Randomized, Controlled Trial of Naproxen and Celecoxib. Arch of Neur. 2008;65(7): 896-905.
2. deAbajo FJ, et al. Risk of upper GI tract bleeding associated with SSRI and Venlafaxine therapy: Interaction with NSAIDs and effect of Acid-suppressing agents. Arch of General Psychiatry. 2008;65(7):795-803.