March 23, 2015
The antiepileptic drug levetiracetam showed promise in reversing cognitive decline in elderly individuals at high risk of dementia, according to a new study.
Johns Hopkins University researchers administered 3 doses of levetiracetam or placebo to 54 patients with amnestic mild cognitive impairment (aMCI) — a transitional condition between normal aging and the symptomatic presentation clinical dementia — and 17 healthy controls before measuring their performances on memory tasks. Treatment with very low doses of levetiracetam reduced activation in the hippocampus to levels seen in healthy older adults and improved memory function in patients with aMCI, according to study lead author Dr. Arnold Bakker, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins.
The highest of the 3 doses, which was closest to the clinically effective range for epilepsy but still below it, was not effective in normalizing brain signals and improving memory function, said Dr. Bakker. “This suggested that only the very low doses of levetiracetam used in this study were effective in normalizing brain imaging signals and improving memory function,” he explained.
Patients at increased risk of developing dementia due to Alzheimer’s disease show hyperactivity in the hippocampus, an area of the brain that is critically important for memory function, said Dr. Bakker.
“Amnestic MCI causes memory problems that are worse than expected for a person’s age,” continued Dr. Bakker, who said the study investigated the functional significance of hyperactivity in the hippocampus and determined if treatment with low-dose levetiracetam would reduce the increased activation and improve memory function, as it has been shown to do in animal models.
Dr. Bakker was a little surprised levetiracetam’s effect in patients was as consistent as it was in animal models, which were given similarly low doses of the drug. “This strong similarity between the results from animal studies and human studies is a rarity that has plagued the field of therapeutic development for Alzheimer’s in recent years,” he said. “In this case, the parallel with animal research provides strong support for the findings.”
As the animal studies showed, levetiracetam’s therapeutic window to treat overactivation in the hippocampus is at much lower doses than those prescribed for the treatment of epilepsy, noted Dr. Bakker.
More studies are needed to test the efficacy and benefit of levetiracetam treatment before recommendations can be made for patients, according to Dr. Bakker, who said a longer-term pivotal trial registered by the U.S. Food and Drug Administration will begin late this year.
The study was published in the journal NeuroImage: Clinical.
1. Bakker A, Albert MS, Krauss G, Speck CL, Gallagher M. Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance. NeuroImage: Clinical. 2015;7:688-698.