Do NSAIDs prevent Alzheimer's disease? And, if so, why? The epidemiological evidence

Given the looming burden of AD, pharmacologic regimens that could delay or even prevent onset of AD would offer tremendous benefits to the public's health. A growing body of evidence, reviewed here, suggests that use of NSAIDs may afford such protection. The only way to demonstrate such protection conclusively is to conduct randomized, double-blind, placebo-controlled prevention trials. At least one such trial is underway, but its data will not be available for a number of years. The available observational data suggest that differences should emerge between the NSAID-treated and placebo-treated groups, but that these differences will not be apparent within the first few years of the trial. Any benefits of NSAIDs, however, will ultimately have to be weighed against the risks associated with their sustained use. NSAIDs have the potential to cause serious side effects when used at high doses or over prolonged periods. Conventional NSAIDs can cause renal and gastro-intestinal complications, including silent gastrointestinal bleeds that can be deadly, especially in the elderly. Such complications might be mitigated if the posited neuroprotective effect of NSAIDs is maintained at low doses, as the epidemiologic data suggest. The COX-2 inhibitors may also be helpful in this regard. However their potential role is at this point still conjectural and their safety when administered to older people for years has not yet been demonstrated. Data from on-going trials, and especially the recently initiated primary prevention trial, should shed light on the relative risks and benefits of these different options and illuminate which could possibly be used as part of a comprehensive strategy to prevent AD.