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Neurobiol Aging. 2008 May;29(5):716-23. Epub 2006 Dec 20.

Glucocorticoid receptor variant and risk of dementia and white matter lesions.

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  • 1Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.



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.


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.


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.


Our findings suggest a protective effect of the ER22/23EK allele on the risk of dementia and white matter lesions.

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