Cholesterol-modifying strategies for Alzheimer's disease.

The link between cholesterol and Alzheimer's disease (AD) is indicated by genetic, epidemiological, experimental and clinical evidence, although the relationship is far from simple or straightforward. Compared with extracerebral cholesterol, little is known about brain cholesterol homeostasis. In addition, current diagnostic criteria for AD exclude a priori the pathogenic participation of vascular factors (to which cholesterol is traditionally associated), and require modifications. Randomized controlled trials suggest that the dementia stage of AD may already be too late for significant benefits of statin therapy, emphasizing the importance of early diagnosis and treatment. Cholesterol-modifying strategies may be more effective in dementia/AD prevention. Since cholesterol is only one piece of the dementia/AD puzzle, integrative interventions (lifestyle-related and, when necessary, pharmacologic) focusing on overall risk instead of individual risk factors may bring more benefit to individuals at risk.