Lower Alzheimer's risk with NSAIDs not due to anti-amyloid action
NSAIDs are equally effective in reducing the risk of Alzheimer's disease (AD), regardless of their effects on a brain protein linked with the disease, a new study has shown.(1) This is the second recent study to show that the protective effect of NSAIDs is probably unrelated to this effect.(2)

AD is associated with deposition in the brain of a protein, amyloid beta peptide. Some NSAIDs, including ibuprofen, have been shown to inhibit this process and are known as Selective Amyloid-Lowering Agents (SALAs). If this property is clinically meaningful, SALAs may be more effective in reducing the risk of AD than non-SALA alternatives.

The latest study pooled the results of six earlier prospective studies to form a group of 13,499 people who were initially free of dementia. Of these, 820 developed AD over a period of 5 - 15 years. Comparing those who did and did not develop AD, the use of any NSAID was associated with a 23 per cent lower risk of developing AD; ibuprofen accounted for more than half of all NSAID use. When the NSAIDs were divided into SALAs and non-SALAs, the difference between them was not statistically significant. This study also showed that paracetamol was not associated with a lower risk of AD.

These findings are consistent with the earlier study, which retrospectively compared SALAs and non-SALAs prescribed for 49,349 people who


developed AD and 196,850 who did not. Although there were no differences in risk reduction between the two types of NSAID, the use of any NSAID for more than 5 years was associated with a 24 per cent reduced risk of AD. For ibuprofen, the risk was reduced by 44 per cent.

Together with previously published studies, the balance of data now shows there is no difference between SALA and non-SALA NSAIDs in their protective effect against AD. This suggests that the mechanism of action does not involve lowering amyloid beta peptide. Further prospective studies are needed to establish the balance of risks and benefits associated with NSAIDs taken to reduce the risk of AD.


References
1. Szekely CA, Green RC, Breitner JC et al. No advantage of Aß42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology 2008;70:2291-8
2. Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDS ion the development of Alzheimer's disease. Neurology 2008;70:1672-7

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