Fran Lowry

July 26, 2011

July 26, 2011 (Paris, France) — Levetiracetam, a drug that is used to treat epilepsy, decreases hippocampal hyperactivity in patients with amnestic mild cognitive impairment (aMCI) and may prove to be useful in preventing or slowing the progression to Alzheimer's disease, researchers say.

"Hippocampal hyperactivity contributes to memory problems, and we have discovered through basic research that very low doses of levetiracetam, much lower than would ever be prescribed for epilepsy, were successful for controlling this hyperactivity," senior author Michela Gallagher, MD, Krieger-Eisenhower Professor of Psychological and Brain Sciences at The Johns Hopkins University, Baltimore, Maryland, told Medscape Medical News.

Dr. Michela Gallagher

The results show that hippocampal hyperactivity in aMCI is not beneficial, as was previously suggested, but contributes to more to memory impairment, Dr. Gallagher said.

"This turns upside down the idea that greater activation in the brain is serving a beneficial purpose. Instead, this greater activation actually seems to be part of the dysfunction that underlies the memory problems," she observed.

"This greater brain activity might be like having your foot on the accelerator if you are on the path to Alzheimer's disease. We need to do additional clinical research, and in fact, we are planning a longer clinical trial to make sure that in the long term, this is a beneficial treatment that has no harmful effects," she said.

The results were presented here at the Alzheimer's Association International Conference 2011.

'Foot on the Accelerator'

In the study, Dr. Gallagher and her colleagues assessed whether levetiracetam treatment decreased hippocampal hyperactivity, particularly the hyperactivity localized to the CA3 subfield of the hippocampus, and improved memory in patients with early aMCI.

They used a placebo-controlled, randomized, crossover design in which 17 aMCI patients and a similar number of healthy age-matched controls completed two 8-week treatment phases separated by a 4-week washout period. The control subjects were given placebo during both treatment phases, whereas patients with aMCI were given placebo during the first treatment phase and low-dose levetiracetam, 125 mg twice daily, during the second treatment phase.

After 2 weeks in each treatment phase, the researchers evaluated the subjects' memory and conducted functional magnetic resonance imaging of their brains. The imaging was done while the subjects were performing a hippocampal-dependent task so that memory errors could be assessed.

They found that levetiracetam brought hippocampal hyperactivity down into the normal range in subjects with aMCI and that their memory performance was also improved to the level of the healthy controls.

Interesting but Very Preliminary

Invited to comment on this study by Medscape Medical News, William Thies, PhD, the chief medical and scientific officer of the Alzheimer's Association, called it "an interesting but very preliminary study.

"There is a small but growing body of research that is looking at seizure and seizure-like activity in the brain and its relationship to Alzheimer's disease," he said. "We are pleased to see some of this material reported at the Alzheimer's Association International Conference this year."

But, he cautioned, "given the small size and very short duration of this particular study, there are still many unanswered questions. We still do not know if the effect seen here will be sustained over time, nor if we will see the same results in larger groups of study participants.

"That said, while this work is preliminary, it points to the value of continuing to investigate excess brain activity and its relationship to Alzheimer's," he added.

This study was funded by the National Institutes of Health. Dr. Gallagher reports a financial relationship with AgeneBio. Dr. Thies has disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2011: Abstract P4-349. Presented June 20, 2011.

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