Effects of Simvastatin on Cerebrospinal Fluid Biomarkers and Cognition in Middle-Aged Adults at Risk for Alzheimer's Disease

Abstract

Background:

Statins reduce amyloid-β (Aβ) levels in the brain and cerebrospinal fluid (CSF) in animals and may thereby favorably alter the pathobiology of AD. It is unclear if statins modify Aβ metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD.

Methods:

In a 4-month randomized, double-blind, controlled study, we evaluated the effects of simvastatin 40 mg daily vs. placebo on CSF Aβ42 levels and cognition in 57 asymptomatic middle-aged adult children of persons with AD.

Results:

Compared to placebo, individuals randomized to simvastatin for 4 months had similar changes in CSF Aβ42 (p=0.344) and total tau levels (p=0.226), yet greater improvements in some measures of verbal fluency (p=0.024) and working memory (p=0.015). APOE4 genotype, gender, and vascular risk factors were associated with CSF biomarker levels, but did not modify treatment effects.

Conclusion:

In asymptomatic middle-aged adults at increased risk for AD, simvastatin use improved selected measures of cognitive function without significantly changing CSF Aβ42 or total tau levels. Further studies are needed to clarify the impact of higher dose and/or longer duration statin therapy on not only Aβ metabolism, but also other preclinical processes related to the development of AD.