Glucocorticoid receptor variant and risk of dementia and white matter lesions.
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.
van Rossum
Elisabeth F C
EF
Department of Internal Medicine, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
de Jong
Frank Jan
FJ
Koper
Jan W
JW
Uitterlinden
André G
AG
Prins
Niels D
ND
van Dijk
Ewoud J
EJ
Koudstaal
Peter J
PJ
Hofman
Albert
A
de Jong
Frank H
FH
Lamberts
Steven W J
SW
Breteler
Monique M B
MM
D000368:Aged; D000369:Aged, 80 and over; D015897:Comorbidity; D003704:Dementia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
D011965:Receptors, Glucocorticoid