Source: Nature
Date: 31 March 2004

Liquorice extract sweetens old age

Carbenoxolone could aid verbal memory

HELEN R. PILCHER

A drug derived from liquorice may boost brain function and slow age-related memory loss, research suggests. Carbenoxolone, which is traditionally used to soothe ulcers, improves mental functioning in healthy elderly men and cognitively impaired diabetic patients.

The drug slows the sort of memory decline that occurs with normal ageing, says Jonathan Seckl from the University of Edinburgh, who led the study. It may, for example, help people to remember random words or recall what they did at the weekend.

It could also slow the early stages of Alzheimer's disease, says Seckl, although this has yet to be tested. The early stages of dementia are indistinguishable from normal memory loss, so the drug could be given to stave off symptoms.

Ten healthy elderly men, without any memory impairment, took carbenoxolone three times a day, the team report in Proceedings of the National Academy of Sciences1. Four weeks later, the subjects performed about 10% better on tests of verbal fluency (the ability to use and recall certain words) than nonmedicated controls. "Carbenoxolone boosts a specific verbal aspect of their memory," says Seckl.

The drug also improved word recall in 12 patients with type-2 diabetes who had already developed memory problems. Their scores also went up by about 10%.

Around half of elderly diabetics develop memory problems as chronically high blood sugar levels take their toll on the functioning of the brain. Over 170 million people worldwide suffer from diabetes.

Stressed out

Age-related memory decline is thought to be triggered by chronic stress, such as that caused by a long-term illness. This raises levels of the stress hormone cortisol in the brain. Humans with chronically high cortisol levels have smaller hippocampi - a brain structure linked with learning and memory - and develop memory problems, explains Seckl. Fortunately, the same problems are not thought to be caused by the wear and tear of everyday life.

Carbenoxolone works by lowering levels of cortisol in the brain, says Seckl. The drug binds to proteins in the hippocampus where it is thought to trigger the expression of genes that aid learning and memory.

"The study confirms that the aged brain can respond to changes in stress hormone levels," says Sonia Lupien from Douglas Hospital McGill University, Montreal, who studies the effects of stress on memory. And that indicates that this kind of memory loss is not permanent, she says: "It shows that the cells are not dead and the changes that some people think are irreversible are not."

The drug cannot be taken alone. Carbenoxolone raises blood pressure, so subjects also took an anti-hypertensive medicine. Both drugs are well tested so they should be safe to prescribe long term, says Seckl.

The team is now planning larger clinical trials.

References

Seckl, J. R. et al. P.N.A.S., published online, doi:10.1073/pnas.0306996101 (2004).

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