The differences in cognitive function during the aging process have been ascribed to variations in long-term glucocorticoid exposure.
11 beta-hydroxysteroid dehydrogenase type 1 (11-HSD1) regenerates the active glucocorticoid cortisol from circulating inert cortisone. This amplifies the intracellular glucocorticoid levels in some tissues.
In this study, investigators from Edinburgh, Scotland, demonstrated that that 11-HSD1, but not 11-HSD2, mRNA is expressed in the human hippocampus, frontal cortex, and cerebellum.
The team performed 2 randomized, double-blind, placebo-controlled crossover studies.
|Carbenoxolone improved verbal fluency after 4 weeks.|
|Proceedings of the National Academy of Sciences|
They found that the administration of the 11-HSD inhibitor carbenoxolone (100 mg 3 times per day) improved verbal fluency after 4 weeks in 10 healthy elderly men.
The investigators also found that this dose of carbenoxolone improved verbal memory after 6 weeks in 12 patients with type 2 diabetes.
Carbenoxolone has been reported to enhance hepatic insulin sensitivity; however there were no changes in glycemic control, serum lipid profile, or plasma cortisol in this study.
Dr Thekkepat Sandeep and colleagues concluded, "11-HSD1 inhibition may be a new approach to prevent/ameliorate cognitive decline".