Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
JAMA. 2008 Jul 16;300(3):287-94. doi: 10.1001/jama.300.3.287.

Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial.

Author information

  • 1Department of General Pediatrics, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.

Abstract

CONTEXT:

Neurofibromatosis type 1 (NF1) is among the most common genetic disorders that cause learning disabilities. Recently, it was shown that statin-mediated inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase restores the cognitive deficits in an NF1 mouse model.

OBJECTIVE:

To determine the effect of simvastatin on neuropsychological, neurophysiological, and neuroradiological outcome measures in children with NF1.

DESIGN, SETTING, AND PARTICIPANTS:

Sixty-two of 114 eligible children (54%) with NF1 participated in a randomized, double-blind, placebo-controlled trial conducted between January 20, 2006, and February 8, 2007, at an NF1 referral center at a Dutch university hospital.

INTERVENTION:

Simvastatin or placebo treatment once daily for 12 weeks.

MAIN OUTCOME MEASURES:

Primary outcomes were scores on a Rey complex figure test (delayed recall), cancellation test (speed), prism adaptation, and the mean brain apparent diffusion coefficient based on magnetic resonance imaging. Secondary outcome measures were scores on the cancellation test (standard deviation), Stroop color word test, block design, object assembly, Rey complex figure test (copy), Beery developmental test of visual-motor integration, and judgment of line orientation. Scores were corrected for baseline performance, age, and sex.

RESULTS:

No significant differences were observed between the simvastatin and placebo groups on any primary outcome measure: Rey complex figure test (beta = 0.10; 95% confidence interval [CI], -0.36 to 0.56); cancellation test (beta = -0.19; 95% CI, -0.67 to 0.29); prism adaptation (odds ratio = 2.0; 95% CI, 0.55 to 7.37); and mean brain apparent diffusion coefficient (beta = 0.06; 95% CI, -0.07 to 0.20). In the secondary outcome measures, we found a significant improvement in the simvastatin group in object assembly scores (beta = 0.54; 95% CI, 0.08 to 1.01), which was specifically observed in children with poor baseline performance (beta = 0.80; 95% CI, 0.29 to 1.30). Other secondary outcome measures revealed no significant effect of simvastatin treatment.

CONCLUSION:

In this 12-week trial, simvastatin did not improve cognitive function in children with NF1. Trial Registration isrctn.org Identifier: ISRCTN14965707.

Comment in

PMID:
18632543
[PubMed - indexed for MEDLINE]
PMCID:
PMC2664742
Free PMC Article

Images from this publication.See all images (2)Free text

Figure 1
Figure 2
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Write to the Help Desk