11ß-Hydroxysteroid dehydrogenase type 1, brain atrophy and cognitive decline

Excess cortisol levels are linked with brain atrophy and cognitive decline in older people. 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) potently amplifies intracellular glucocorticoid action by converting inert cortisone to active cortisol, but any causal importance in brain ageing is unexplo...

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Bibliographic Details
Published in:Neurobiology of aging 2010-10, Vol.33 (1), p.207.e1-207.e8
Main Authors: MacLullich, Alasdair MJ, Ferguson, Karen J, Reid, Louise M, Deary, Ian J, Starr, John M, Wardlaw, Joanna M, Walker, Brian R, Andrew, Ruth, Seckl, Jonathan R
Format: Article
Language:English
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Summary:Excess cortisol levels are linked with brain atrophy and cognitive decline in older people. 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) potently amplifies intracellular glucocorticoid action by converting inert cortisone to active cortisol, but any causal importance in brain ageing is unexplored. We tested the hypotheses that higher systemic 11ß-HSD1 activity predicts brain atrophy and cognitive decline in older men. In a longitudinal study of 41 men (65-70y at baseline) we measured baseline systemic 11ß-HSD1 activity, the urinary 5alpha- and 5beta-tetrahydrocortisol to tetrahydrocortisone ratio (THFs/THE), and assessed change in brain atrophy, white matter lesions and cognitive function over six years. Baseline THFs/THE correlated negatively with baseline hippocampal volumes (left: r=-0.37; right: r=-0.34; p
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2010.09.010