NSAIDs and Alzheimer's Risk

Mindy J Kim-Miller, MD, PhD

Although many studies have examined the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the risk of developing Alzheimer’s disease, the results remain confusing.

Some of the common NSAIDs used in these studies include aspirin, acetaminophen (Tylenol), ibuprofen (Advil, Motrin), celecoxib (Celebrex), naproxen (Aleve), indomethacin (Indocin), and sulindac (Clinoril).

One report published in June of 2008 examined data from six previous studies and found that all NSAIDs appear to be equally effective at preventing Alzheimer’s. Of the 13,499 participants in these studies, 820 developed Alzheimer’s. Most of the participants the six studies examined were over 64 years old, and those who developed Alzheimer’s were usually over 80 years old.

People who used any type of NSAID had a 23% reduction in the risk of developing the disease compared with those who never used the drugs. The only exception was acetaminophen, which did not significantly decrease the risk.

The six studies varied on the definition of NSAID use. Three studies defined it as current use. One study looked at current use plus use over the previous 2 weeks. Another study assessed use over the prior 2 years, and one defined use as current or former use of four or more doses per week for 1 month or longer.
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In contrast to that report, an earlier study had found mixed results for different kinds of NSAIDs, with ibuprofen showing the most protective effect against Alzheimer’s.

Yet other studies had reported no significant benefit from NSAIDs on either cognitive decline or Alzheimer’s disease risk.

To make the story even more confusing, a recent study published in April of 2009 claimed that heavy NSAID use among people 65 and older is associated with an increased risk of developing dementia. Of the 2,736 participants at the start of the study, 476 developed dementia and 356 developed Alzheimer’s during the 12-year study. Heavy NSAID users were 66% more likely to develop dementia and 57% more likely to develop Alzheimer’s compared to non-users. Heavy NSAID use was defined as taking at least 500 or more standard daily doses during a two-year period.

At this point, “everything in moderation” might be a good way to summarize these studies. Some NSAID use may help reduce the risk of developing Alzheimer’s disease, but too much NSAID use may actually increase the risk. In order to get a clearer, more conclusive understanding, there will need to be further research exploring the relationship between NSAIDs and the development of dementia.

ADAPT Research Group. Cognitive function over time in the Alzheimer’s disease anti-inflammatory prevention trial (ADAPT): Results of a randomized, controlled trial of naproxen and celecoxib. Arch Neurol 2008 Jul; 65(7): 896-905.
Breitner J, et al. Risk of dementia and AD with prior exposure to NSAIDS in an elderly community-based cohort. Neurology 2009 Apr; 72(17): DOI: 10.1212/WNL.0b013e3181a18691.
Szekely CA, et al. No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology. 2008 Jun; 70(24): 2291-8.
Vlad SC, et al. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008 May; 70: 1672-7.

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