Patients with Alzheimer's disease may be particularly susceptible to adverse effects of statins

Abstract

In epidemiological, cross-sectional studies, treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) prevented to a large extent the development of Alzheimer's disease (AD), but the results of randomized, placebo-controlled studies, focused on statin therapy in patients with ischemic heart disease (IHD), are at variance. Nonetheless, data from epidemiological, longitudinal studies in humans as well as studies on transgenic mouse models and cultured neuronal cell lines indicate that cholesterol may contribute to the pathogenesis of AD. Statins have proven therapeutic and preventive effects in IHD and other vascular diseases in man. They generally are well tolerated, but some adverse effects, probably due to antiproliferative and proapoptotic properties of the statins, are matters of concern. AD patients may be extrasusceptible to adverse effects of statins due to preexisting aberrations in signal transduction and energy metabolism in the neurons and a perturbed cholesterol metabolism in the brain. This problem might be addressed in randomized, double-blind studies with statins in AD. The statins differ from each other in several aspects, and they are not considered to be therapeutically interchangeable. It could be fruitful to use both a placebo and two different types of statins, i.e. an essentially hydrophilic statin and a lipophilic statin, in a double-blinded fashion, and to compare the effects on the cognitive decline in AD.