Glucocorticoid receptor variant and risk of dementia and white matter lesions

van Rossum, Elisabeth F.C.; de Jong, Frank Jan; Koper, Jan W.; Uitterlinden, André G.; Prins, Niels D.; van Dijk, Ewoud J.; Koudstaal, Peter J.; Hofman, Albert; de Jong, Frank H.; Lamberts, Steven W.J.; Breteler, Monique M.B.

doi:10.1016/j.neurobiolaging.2006.11.016

« Previous Next »Neurobiology of Aging
Volume 29, Issue 5 , Pages 716-723, May 2008

Glucocorticoid receptor variant and risk of dementia and white matter lesions

Elisabeth F.C. van Rossum
- Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
- These authors contributed equally.
Frank Jan de Jong
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
- Department of Neurology, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
- These authors contributed equally.
Jan W. Koper
- Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
André G. Uitterlinden
- Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
Niels D. Prins
- Department of Neurology, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
Ewoud J. van Dijk
- Department of Neurology, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
Peter J. Koudstaal
- Department of Neurology, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
Albert Hofman
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
Frank H. de Jong
- Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
Steven W.J. Lamberts
- Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
Monique M.B. Breteler
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
- Corresponding author. Tel.: +31 10 4087930; fax: +31 10 4089382.

Received 4 September 2006; received in revised form 13 November 2006; accepted 19 November 2006. published online 22 December 2006.

Abstract

Objective

Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor gene variant (ER22/23EK) is related to relative glucocorticoid resistance. We investigated whether the ER22/23EK allele is associated with dementia and structural brain abnormalities.

Methods

This study was performed in two prospective population-based cohort studies among elderly. The first study included 6034 participants who were screened for dementia (mean follow-up 5.8 years). The second study included 1011 elderly subjects with an MRI at baseline and follow-up. The ER22/23EK allele was assessed for association with dementia, cognitive function and white matter lesions.

Results

The ER22/23EK allele was associated with a decreased risk of dementia. Among non-demented participants, ER22/23EK-carriers had a better performance on psychomotor speed tests than non-carriers. No differences were found in memory function between genotypes. In addition, both presence and progression of white matter lesions was lower in ER22/23EK-carriers. No association was found with brain atrophy on MRI.