Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease

Statins reduce amyloid-beta (Abeta) 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 Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD. In a 4-month ran...

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Bibliographic Details
Published in:	Journal of Alzheimer's disease Vol. 13; no. 2; p. 187
Main Authors:	Carlsson, Cynthia M, Gleason, Carey E, Hess, Timothy M, Moreland, Kimberly A, Blazel, Hanna M, Koscik, Rebecca L, Schreiber, Nathan T N, Johnson, Sterling C, Atwood, Craig S, Puglielli, Luigi, Hermann, Bruce P, McBride, Patrick E, Stein, James H, Sager, Mark A, Asthana, Sanjay
Format:	Journal Article
Language:	English
Published:	Netherlands 01-03-2008
Subjects:	Adult Aged Alzheimer Disease - drug therapy Alzheimer Disease - genetics Amyloid beta-Peptides - cerebrospinal fluid Amyloid beta-Peptides - drug effects Anticholesteremic Agents - pharmacology Anticholesteremic Agents - therapeutic use Apolipoprotein E4 - genetics Cognition Disorders - cerebrospinal fluid Cognition Disorders - diagnosis Cognition Disorders - epidemiology Double-Blind Method Female Genetic Predisposition to Disease Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Lipoproteins - blood Male Middle Aged Neuropsychological Tests Risk Factors Severity of Illness Index Simvastatin - pharmacology Simvastatin - therapeutic use
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Summary:	Statins reduce amyloid-beta (Abeta) 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 Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD. In a 4-month randomized, double-blind, controlled study, we evaluated the effects of simvastatin 40 mg daily vs. placebo on CSF Abeta42 levels and cognition in 57 asymptomatic middle-aged adult children of persons with AD. Compared to placebo, individuals randomized to simvastatin for 4 months had similar changes in CSF Abeta42 (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. In asymptomatic middle-aged adults at increased risk for AD, simvastatin use improved selected measures of cognitive function without significantly changing CSF Abeta42 or total tau levels. Further studies are needed to clarify the impact of higher dose and/or longer duration statin therapy on not only Abeta metabolism, but also other preclinical processes related to the development of AD.
ISSN:	1387-2877
DOI:	10.3233/JAD-2008-13209