Statins to treat Alzheimer's disease: an incomplete story

The link between cholesterol and Alzheimer's disease (AD) has been explored for almost two decades. The link stems from the observation that atherosclerotic heart disease increases the risk for AD and that people expiring from coronary artery disease had AD changes in their brains. Cholesterol is a cofactor of amyloid deposition, with substantial evidence showing that high cholesterol diets in animal models can accelerate amyloidogenesis. This link led investigators to posit the use of cholesterol-lowering agents as treatments for AD and cognitive decline. Indeed, the epidemiological data suggest that cholesterol-lowering agents may reduce the risk of developing AD. Early pilot studies suggested that statins may be useful as treatments for AD because of a reduction in the rates of decline. Recent reports of simvastatin and atorvastatin assessed in large randomized, double-blind, placebo-controlled multicenter trials have not confirmed a clinically demonstrable cognitive benefit for statins in the treatment of AD. This article will discuss the results of one of these trials and explore the reasons behind why the multicenter trials may not have been positive and the growing disparity between preclinical/epidemiological benefit and a lack of clinical efficacy.