More Data for Neuroprotective Effect of NSAIDs
Data to date suggest that NSAIDs, including aspirin, do not affect the course of Alzheimer’s disease in those with an established diagnosis (see, for instance, here and here). However, the potential of NSAIDs to prevent or delay the onset of dementing illnesses is another matter. Recently investigators at Johns Hopkins found that the use of NSAIDs, but not aspirin, lowered the risk of dementia overall—and in particular AD—among participants in the Cardiovascular Health Cognition Study.* Closer examination of the data revealed that the protective benefit of NSAIDs was confined to those individuals with an ApoE4 allele but did not appear to be attributable to the suppression of Aβ1-42 amyloid.
Now comes a review of Veterans Affairs records in the latest issue of Neurology, which supports the long-term use of NSAIDs to reduce the risk of AD. These data were particularly compelling for ibuprofen (or what I like to call God’s gift to me). Also, like the Hopkins study, a distinction was not observed between NSAIDs that suppress the formation of Aβ1-42 amyloid (ie, ibuprofen, indomethacin, sulindac, and diclofenac) and those that don’t (eg, naproxen, etodolac).
But most important, the benefit of NSAIDs appeared to be associated with the duration of their prescription (determined from VA pharmacy records). The authors found that the odds of AD decreased from 0.98 with ≤1 year of NSAID use to 0.76 with ≥5 years, in the nearly 250,000 individuals identified. A similar, but more pronounced, effect was observed with the use of arylpropionic acids, such as ibuprofen or naproxen (≤1-year OR = 1.00; ≥5-year OR = 0.63). However, no protective benefit was observed with the use of COX-2 inhibitors or nonacetylated NSAIDs (eg, salsalate).†
The authors acknowledge a number of limitations in their review study, including potential errors in diagnostic coding, medical confounders (eg, education, tobacco use), and actual NSAID exposure. It’s entirely possible that patients did not take their prescribed medications, or that others took undocumented over-the-counter NSAIDs. Also data were not available (understandably) for the ApoE4 allele status of the veterans.
Nevertheless, given these data, the authors conclude that a randomized, prospective trial of long-term NSAID therapy (and ideally ibuprofen) is warranted. The same can also be recommended to assess the risk reduction of Parkinson’s disease with non-aspirin NSAIDs, according to a recent UCLA study.
*Curiously enough, the risk of vascular dementia was not affected by NSAID use.
†What’s old is new again, or is this just the VA? I didn’t know anybody prescribed Disalcid anymore.