Statins to treat Alzheimer’s disease: an incomplete story

Abstract

Evaluation of: Sano M, Bell KL, Galasko D et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 77(6), 556–563 (2011).

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.

Keywords::

• Alzheimer’s disease
• atorvastatin
• cholesterol
• clinical trials
• cognitive decline
• simvastatin
• statins

Financial & competing interests disclosure

MN Sabbagh receives grant/contract support from Pfizer, Eisai, Lilly, BMS, Baxter, Bayer, GE, Genentech and Avid. The grant was supported by NIH-NIA P30 AG019610. MN Sabbagh consults for Takeda, BMS, Bayer, Janssen, Lilly, Eisai, Avid and Amerisciences. MN Sabbagh receives royalties from Amerisciences and Wiley. DL Sparks has received grant support from ISOA and Pfizer for support of the ADCLT in the past. He has been an advisor to Pfizer on the LEADe study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.