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

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Keywords Alzheimer's disease, Dementia, Glucocorticoid receptor, Polymorphism, White matter lesions
Persistent URL dx.doi.org/10.1016/j.neurobiolaging.2006.11.016, hdl.handle.net/1765/29284
Journal Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology
van Rossum, E.F.C, de Jong, F.J, Koper, J.W, Uitterlinden, A.G, Prins, N.D, van Dijk, E.J, … Breteler, M.M.B. (2008). Glucocorticoid receptor variant and risk of dementia and white matter lesions. Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology, 29(5), 716–723. doi:10.1016/j.neurobiolaging.2006.11.016