Treatment with carbenoxolone is associated with improved verbal fluency and verbal memory in elderly men, according to a report by UK researchers in an online edition of Proceedings of the National Academy of Sciences, published on March 29th.

According to Dr. Jonathan R. Seckl of the University of Edinburgh and colleagues, chronic increases in hippocampal glucocorticoid levels have been associated with age-related cognitive impairment.

The enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11B-HSD1)increases glucocorticoid activity in the brain of rats and the team posited that carbenoxolone, an 11B-HSD1 inhibitor derived from licorice root, would protect the brain from glucocorticoid
neurotoxicity.

They therefore conducted placebo-controlled, crossover studies of carbenoxolone 100 mg three times a day in elderly men. In 10 healthy men ages 55 to 75 years, four weeks of treatment with carbenoxolone improved scores on the Controlled Word Association Test, a measure of verbal fluency.

In 12 men with well-controlled type 2 diabetes, treatment for 6 weeks was associated with improved verbal memory, according the Rey Auditory-Verbal Learning Test scores.

Amiloride was co-administered to prevent renal mineralocorticoid
excess. There were no adverse effects, and blood pressure, plasma sodium and cortisol did not differ between study phases.

"The effect magnitude of up to 0.5 SD seems to be a worthwhile,
clinically significant attainment," the researchers point out. "11B-HSD1 may therefore afford a mechanistically tractable new therapeutic target to prevent or ameliorate age-associated cognitive dysfunction in healthy elderly subjects and in patients with type 2 diabetes."

Proc Natl Acad Sci USA 2004.

NEW YORK (Reuters Health) Mar 29

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