A study led by a Johns Hopkins neuroscientist and published in the May 10 issue of the journal Neuron suggests a potential new therapeutic approach for improving memory and interrupting disease progression in patients with a form of cognitive impairment that often leads to full-blown Alzheimer's disease. The focus of the study was "excess brain activity" commonly associated with conditions that cause mild cognitive decline and memory loss, and are linked to an increased risk of Alzheimer's. Previously, it had been thought that this neural hyperactivity in the hippocampus（海马） was the brain's attempt to compensate for a weakness in forming new memories. Instead, the team found that this excess activity is contributing to conditions such as amnestic（遗忘的） mild cognitive impairment (aMCI), in which patients' memories are worse than would be expected in healthy people the same age.

"In the case of aMCI, it has been suggested that the increased hippocampal activation may serve a beneficial function by recruiting additional neural 'resources' to compensate for those that are lost," explains lead author Michela Gallagher, the Krieger-Eisenhower Professor of Psychological and Brain Sciences in the Johns Hopkins University's Krieger School of Arts and Sciences. "However, animal studies have raised the alternative view that this excess activation may be contributing to memory impairment."

To test how a reduction in that hippocampal activity would affect human patients with aMCI, Gallagher's team administered a low dose of a drug clinically used to treat epilepsy（癫痫） . The goal was to reduce the test subjects' activity to levels that were similar to those of healthy, age-matched subjects in a control group. They used functional magnetic resonance imaging both to determine the levels of excess activity, and the reduction of it by way of the drug.

Gallagher and her team found that those subjects who had been treated with an effective dose of the drug did better on a memory task, pointing to the therapeutic potential of reducing this excess activation of the hippocampus in patients with aMCI. These findings in human patients with aMCI are the first to clinically demonstrate that over activity in the hippocampus has no benefit for cognition, and are consistent with Gallagher's research in an animal model of memory loss: aged rodents.

The findings may have broad clinical implications because increased hippocampal activation occurs not only in patients with aMCI, but also in other conditions of risk, such as familial Alzheimer's disease (AD).

Research in mouse models of familial AD conducted at the Gladstone Institutes of San Francisco has identified mechanisms of the brain that contribute to abnormal excitatory brain activity, as reported in a paper published in the April 27 issue of the journal Cell. In addition, the results of other studies in mice using the same drug used in aMCI patients were presented at last year's International Congress on Alzheimer's disease in Paris, showing both improved memory performance and neuronal function in the hippocampus.