Anti-inflammatory drugs

Older news items (pre-2010) brought over from the old website

Pain relievers don’t prevent Alzheimer's in the very elderly

In contrast to a number of studies indicating benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing Alzheimer’s, a large, long-running study following 2,736 members of a healthcare delivery system for 12 years, has revealed that not only did use of these drugs not reduce the risk of developing dementia, the risk among these very elderly (most were over age 83 when they developed dementia) was 66% higher among heavy NSAID users than among people who used little or no NSAIDs. Heavy use was defined as having prescriptions for NSAIDs at least 68% of the time in two years. Although this seems to contradict earlier research, it may be consistent with the theory that NSAID use delays the onset of Alzheimer's – thus, studies of younger NSAID users would show fewer Alzheimer's cases, while groups of older people might show more cases.

Breitner, J.C.S. et al. 2009. Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology, Published online April 22, 2009.

Inflammatory response to infection and injury may worsen dementia

Systemic inflammation – inflammation in the body as a whole – is known to have direct effects on brain function, but there has been little research into the impact of systemic inflammation on the progress of dementia and neurodegenerative diseases. Now, in a study to mimic the effect of bacterial infection in people with dementia, a mouse study has revealed that that the inflammatory response to infection in mice with prior neurodegenerative disease leads to exaggerated symptoms of the infection, causes changes in memory and learning and leads to accelerated progression of dementia.

Cunningham, C. et al. In press. Systemic Inflammation Induces Acute Behavioral and Cognitive Changes and Accelerates Neurodegenerative Disease. Biological Psychiatry.

Anti-inflammatory drugs do not improve cognitive function in older adults

Previous studies have suggested that nonsteroidal anti-inflammatory drugs are associated with a lower risk of developing Alzheimer’s. A clinical trial involving over 2000 older adults (70+) with a family history of Alzheimer’s disease compared a twice daily treatment of 200 milligrams of either the NSAID celecoxib, or the NSAID naproxen sodium, or a placebo. The trial lasted from March 2001 to December 2004. The study found not only that NSAIDs didn’t improve cognitive function, but that naproxen (but not celecoxib) was associated with significantly lower cognitive performance.

ADAPT Research Group. 2008. Cognitive Function Over Time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): Results of a Randomized, Controlled Trial of Naproxen and Celecoxib. Archives of Neurology, 65(7), (doi:10.1001/archneur.2008.65.7.nct70006).

Ibuprofen linked to reduced risk of Alzheimer's disease

A very large five-year study of older veterans (55+) has found that those who  used ibuprofen for more than five years were more than 40% less likely to develop Alzheimer’s disease. Results also showed that the longer ibuprofen was used, the lower the risk for dementia. Other types of NSAIDs, such as indomethacin, were associated with a 25% reduced risk, however others, such as celecoxib, didn’t show any benefit. There was no obvious connection between those which were associated with reduced risk and those that weren’t. It may be that the effect is a product of some other cause.

Vlad, S.C. et al. 2008. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology, 70, 1672-1677.

Ibuprofen, aspirin, naproxen may be equally effective at reducing Alzheimer's risk

And demonstrating that the jury is still out on NSAIDs, a review of six studies has found that people who used NSAIDs had a 23% lower risk of developing Alzheimer’s disease compared to those who never used NSAIDs. The risk reduction did not appear to depend upon the type of NSAID taken. However, the researchers were specifically looking for a difference between those NSAIDs that lower Aβ1-42 amyloid, which was what they didn’t find — and this agrees with the finding of the large veteran study. The findings of this study then may be taken as supporting the view that specific NSAIDs may be of benefit rather than a particular class of them.

Szekely, C.A. et al. 2008. No advantage of Aβ42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology, 70, 2291-2298.

Low dose aspirin does not protect women against cognitive decline

Evidence that aspirin and other anti-inflammatory drugs may protect against dementia has been inconclusive. Now a large, long-running study involving 6,377 women aged 65 years or more, over ten years, has found that those who took low dose aspirin (100 mg on alternate days) performed at similar levels to a placebo group on cognitive tests. However, there was evidence of benefit in one very specific area of cognition: category fluency.

[850] Kang, J H., Cook N., Manson JA., Buring J. E., & Grodstein F.
(2007).  Low dose aspirin and cognitive function in the women's health study cognitive cohort.
BMJ. 334(7601), 987 - 987.

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Conflicting results about benefit of anti-inflammatory drugs

It’s long been known that patients regularly taking nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen, seem to have less risk of developing Alzheimer's. It’s been suggested that this might mean that Alzheimer's is a product of inflammation in the brain, and that damage happens when the microglia, the brain's immune cells, become overactive and attack healthy neurons. A new study of autopsy brain tissue, and of in vitro rat cultures indicates that, on the contrary, what’s happening is that, as microglia age, they lose their ability to protect the brain. Moreover, the latest study into the effects of anti-inflammatory drugs found no benefit for those suffering from Alzheimer’s. Indeed, it is possible that such drugs might exacerbate the problem. It is speculated that microglia may have the potential to both protect and attack neurons. The key may lie in the way microglia interact with beta-amyloid protein.

Anti-inflammatories lower Alzheimer disease–related protein levels in mice

Following earlier research showing three commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) were capable of selectively lowering the levels of Abeta42 (an isoform of the amyloid beta protein) in mice, investigation of 20 commonly used NSAIDs found 8 FDA-approved drugs successfully lowered Abeta42 levels in mice at doses achievable in humans.

Eriksen, J.L. et al. 2003. NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aß42 in vivo. Journal of Clinical Investigation, 112, 440-449.

Anti-inflammatories offer some protection against developing Alzheimer's

A review of 9 observational studies that examined the role of NSAID use in preventing Alzheimer's disease found the pooled relative risk of Alzheimer's disease among users of NSAIDs was 0.72. The risk was 0.95 among short term users (< 1 month), 0.83 among intermediate term (mostly < 24 months) and 0.27 for long term (mostly > 24 months) users. The pooled relative risk in 8 studies of aspirin use was 0.87. It was concluded that NSAIDs offer some protection against the development of Alzheimer's disease.

Etminan, M., Gill, S. & Samii, A. 2003. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. BMJ, 327, 128.

Buildup of amyloid plaques linked to gene inhibition

Examination of genetically engineered mice and of brain tissue from deceased Alzheimer's patients has found that the buildup of amyloid plaques in the brain dramatically inhibits six genes known to be important for the formation of new memories. The finding suggests a new approach to the treatment of Alzheimer’s disease, combining amyloid-lowering treatment with other strategies designed to block the effect of amyloid on these genes.

Dickey, C.A. et al. 2003. Selectively Reduced Expression of Synaptic Plasticity-Related Genes in Amyloid Precursor Protein + Presenilin-1 Transgenic Mice. Journal of Neuroscience, 23, 5219-5226.