Cognitive function in old age but not mood is dependent on a ER22/23EK variation in the glucocorticoid receptor gene. The Leiden 85-plus Study.

Maris Kuningas, Jacobijn Gussekloo, Simon P. Mooijaart, David J. Vinkers, Jelle Jolles, P. Eline Slagboom, Rudi G.J. Westendorp, Diana van Heemst

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Abstract

Cognitive decline in old age and mood have been associated with changes in cortisol
signaling. Cortisol is a stress hormone, which exerts its functions through
mineralocorticoid (MR) and glucocorticoid (GR) receptors. At high cortisol levels, GRs
get fully activated and therefore it is believed that GRs are resposible for the damaging
effects of elevated cortisol. Recently, a ER22/23EK variation in the GR gene was
associated with resistance to cortisol. Within the Leiden 85-plus Study we examined the
relation between the ER22/23EK variation in the GR gene and cognitive function and
mood in old age. In a cross-sectional analysis of 540 participants aged 85 years,
ER22/23EK haplotype carriers and non-carriers did not differ in overall cognition and in
specific domains of cognitive functioning. However, during mean follow-up of 4.2 years,
carriers of the ER22/23EK haplotype had lower attention (2.42 ± 1.19, p=0.043) and
slower decline in delayed recall memory function (0.25 ± 0.10, p=0.008). There was no
effect of the ER22/23EK variation on depressive symptoms, neither cross-sectionally
(0.64 ± 0.52, p=0.22) nor longitudinally (-0.06 ± 0.11, p=0.58). Thus, in elderly subjects
aged 85 years and older cognitive function but not mood is dependent on the ER22/23EK
variation in the GR gene.
Original languageEnglish
PublisherLeiden University
Pages1-18
Number of pages18
Publication statusPublished - 1 Jan 2007

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