Cholesterol level and statin use in Alzheimer disease: I. Review of epidemiological and preclinical studies

Abstract

During the last 2 decades, evidence has accumulated that a high cholesterol level may increase the risk of developing Alzheimer disease (AD). With the global use of statins to treat hypercholesterolemia, this finding has led to the anticipation that statins could prove useful in treating or preventing AD. However, the results of work on this topic are inconsistent: some studies find beneficial effects, but other studies do not. In this first segment of a 2-part review, we examine the complex preclinical and clinical literature on cholesterol level and AD. First, we review epidemiological research on cholesterol level and the risk of AD and discuss the relevance of discrepancies among studies with regard to participants' age and clinical status. Second, we assess studies correlating cholesterol level with neuropathological AD type. The potential molecular mechanisms for the apparent adverse effects of cholesterol on the development of AD are then discussed. Third, we review preclinical studies of statin use and AD. Therefore, this first part of our review provides the background and rationale for investigating statins as potential therapeutic agents in patients with AD, the subject of the second part.

Figure 1. Relationship between outcome and age of participants in studies of cholesterol’s effect on dementia risk and progression

For each balloon, the left-most end is positioned at the mean age at study start, the width represents the follow-up time, and the height represents the cohort size. Red color signifies a positive correlation between cholesterol levels and dementia risk, gray a negative correlation, and blue no correlation. An additional study by Whitmer and colleagues is not included here because the large size of its cohort and long follow-up period would distort the figure.