Epilepsy Drug Improves Memory in Alzheimer's Model, Patients
Researchers have found that it's possible to improve memory, even reverse memory loss, using a drug typically prescribed to treat epilepsy. Although it's still too early to recommend the drug, levetiracetam, to prevent or treat Alzheimer's disease, research results are promising.
Can an epilepsy drug help with Alzheimer's disease?
It is not uncommon for a drug originally developed to treat one disease or condition to be found effective in the treatment or prevention of a completely different ailment. One current example comes to mind; namely, the use of Avastin for breast cancer and for macular degeneration, an eye disease that can result in blindness.
In this new study, the drug in question is levetiracetam, an anticonvulsant that has long been used along with other medications to treat seizures in individuals who suffer with epilepsy. However, investigators have also found that this anticonvulsant may be instrumental in reversing memory loss in Alzheimer's disease.
The results of two studies are reported here. The latest study was conducted in mice under the leadership of Lennart Mucke, MD, professor of neurology and neuroscience at the University of California, San Francisco and director of neurological research at Gladstone Institutes.
Levetiracetam or saline (control) was administered to Alzheimer's mice models, and the researchers noted the following:
- Within 24 hours of giving levetiracetam, the researchers observed that abnormal activity in the neuronal network of the mice, which is critical for memory and other essential brain functions, had declined by 50 percent. In individuals who have Alzheimer's disease, disruptions in these neuronal networks can result in epileptic seizures.
- Two weeks after giving the mice the levetiracetam, the ability of the neurons to communicate with each other improved. Effective communication between neurons is essential for decision making, thinking, and other cognitive functions.
- When the mice were tested in a maze, the treated mice demonstrated better memory and learning when compared with the control mice.
- A number of proteins that are necessary for the healthy functioning of the brain returned to normal levels in the mice treated with levetiracetam.
According to Pascal Sanchez, PhD, a Gladstone postdoctoral fellow, "We are now building on these findings and working to identify the precise mechanism by which this drug reduces brain-network dysfunction and improves memory in our mouse models."
But mice are not the only ones who appear to benefit from levetiracetam when it comes to memory. At Johns Hopkins University, a research team examined the effects of the anticonvulsant on a small group of individuals who had mild cognitive impairment and compared the results with healthy controls.
It's been shown that elevated activity in the hippocampus--an area of the brain involved with memory and other cognitive functioning--is associated with cognitive impairment. The Johns Hopkins researchers found that a low dose of levetiracetam reduced hippocampal activity in mild cognitive impairment to a level similar to that in healthy controls.
The findings of the Johns Hopkins study prompted Mark Baxter, PhD, professor of neuroscience, anesthesiology, and geriatrics and palliative medicine at Mount Sinai School of Medicine to note in a recent article in Trends in Cognitive Science that they point "towards a new treatment strategy for age-related memory impairment by reducing deleterious overactivity of the hippocampus."
So where do scientists go from here? It's not time to start dispensing levetiracetam just yet. "Until larger human trials have been completed," noted Mucke, "we caution against any off-label use of levetiracetam." He is heartened, however, by "the consistency between our findings and those just obtained by our colleagues at Johns Hopkins," and believes "additional clinical trials" are warranted to further explore how this epilepsy drug may help with memory and Alzheimer's disease.
Bakker A et al. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 2012 May 10; 74(3): 467-74
Baxter MG. Quieting the overactive hippocampus restores memory in aging. Trends in Cognitive Science 2012 Jul; 16(7): 360-61
Pascal E et al. Levetiracetam suppresses neuronal network dysfunction and reverse synaptic and cognitive deficits in an Alzheimers disease model. PNAS 2012 Aug; doi:10.1073/pnas.1121081109