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11β-hydroxysteroid dehydrogenase type 1, brain atrophy and cognitive decline
Alasdair M J MacLullich1, Karen J Ferguson, Louise M Reid
1Endocrinology, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, Scotland, UK. a.maclullich@ed.ac.uk
Neurobiology of Aging
|October 22, 2010
Summary
Higher 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity in older men predicts brain atrophy and cognitive decline. This suggests inhibiting 11β-HSD1 may be a viable therapy for brain aging.
Area of Science:
- Neuroendocrinology
- Gerontology
- Brain Aging Research
Background:
- Elevated cortisol is associated with brain atrophy and cognitive impairment in aging individuals.
- 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enhances intracellular cortisol activity, but its role in brain aging is unclear.
Purpose of the Study:
- To investigate if higher systemic 11β-HSD1 activity predicts brain atrophy and cognitive decline in older men.
- To explore the relationship between 11β-HSD1 activity and changes in brain structure and cognitive function over time.
Main Methods:
- Longitudinal study of 41 men aged 65-70 years.
- Measurement of baseline systemic 11β-HSD1 activity using the urinary THF/THE ratio.
- Assessment of brain atrophy (hippocampal and ventricular volumes), white matter lesions, and cognitive function over 6 years.
Main Results:
- Baseline THF/THE ratio negatively correlated with hippocampal volume and positively with ventricular volume and white matter lesions.
- Higher baseline THF/THE ratio predicted increased ventricular volume and decline in processing speed over 6 years.
- Baseline cortisol levels did not predict these changes.
Conclusions:
- Systemic 11β-HSD1 activity is a significant predictor of progressive brain atrophy and cognitive decline in older men.
- Targeting 11β-HSD1 may represent a potential therapeutic strategy for mitigating age-related brain changes.
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