There has been very little good news when it comes to preventing or treating Alzheimer’s disease. Billions have been spent on drug development but there is little, if anything, to show for the effort.
A new study from Johns Hopkins University (Neurolmage: Clinical, online, Feb. 21, 2015) may have discovered an exciting new use for an old drug. Keppra was first approved as an anticonvulsant to treat epilepsy in 2000. In 2008 it became available generically as levetiracetam. That makes the drug quite affordable, though we have received a number of reports from patients that some generic formulations may not work as well as brand name Keppra for preventing seizures.
Now, researchers are reporting that this medication may calm over-activity in parts of the brain that may be responsible for mild cognitive impairment and memory problems. Basically we’re talking about brain fog. When the part of the brain called the hippocampus becomes overactive, it may portend increased deterioration in thinking and memory and eventually lead to full-blown Alzheimer’s disease.
The investigators employed the gold standard format, a randomized, double-blind, placebo-controlled study to test the effects of levetiracetam on the brain. They analyzed data from 54 participants who had been diagnosed with pre-dementia memory loss. They defined these patients as having “amnestic mild cognitive impairment” or aMCI. The remaining 17 volunteers were healthy with normal brain function.
The subjects were given different doses of levetiracetam, ranging from 62.5 mg twice a day to 125 mg twice a day all the way up to 250 mg twice a day. Subjects had their brain activity assessed in the MRI scanner. They were also tested for memory and cognitive performance.
What Was the Outcome of the Research?
And the envelope please! Both low doses of levetiracetam (62.5 and 125 mg) enhanced memory and normalized the over-activity within the hippocampus. In their own words the researchers reported:
“The primary focus in the current study was to assess the effects of treatment with the atypical anti-epileptic, levetiracetam, on memory performance in the scanning task and fMRI [functional magnetic resonance imaging ] signals in aMCI [amnestic mild cognitive impairment] patients. In the current investigation, low doses of levetiracetam (62.5 and 125 mg BID [twice a day]) significantly improved memory performance in the scanning task with attenuation of overactivity, an effect that was statistically significant at 125 mg BID…The current findings further suggest that in the dose range of 62.5-125 mg BID, levetiracetam confers benefit on the network properties of the medial temporal lobe memory system.”
What makes this research intriguing is that they used very low doses of levetiracetam. A standard dosing regimen for epilepsy would be 500 mg twice daily up to a maximum of 3,000 mg a day. The dose used in this dementia study was one-eighth to one-fourth of the lowest dose used to control seizures.
That creates an interesting challenge for physicians who might want to experiment with this drug. It is only available in 250 mg tablets (or greater strengths). The only way a physician could approximate the dose would be to utilize the oral solution (100 mg/ml) and have a pharmacist make the appropriate dosing adjustments and instruct patients accordingly.
What about side effects?
At the very low doses used in this experiment we suspect that adverse reactions related to levetiracetam were probably mild, but the researchers did not describe complications. That may be in part because the study was so short. Nevertheless, we feel it necessary to let readers know what the potential adverse reactions of higher doses used to control epilepsy might be.
Levetiracetam Side Effects
- Fatigue, tiredness, lack of energy
- Digestive upset (nausea, diarrhea, loss of appetite, vomiting)
- Changes in behavior (agitation, anxiety, irritability, hostility, confusion, depression)
- Dizziness, vertigo, unsteadiness
- Sore throat, sinusitis, runny nose, infection
- Rash (requires immediate medical attention)
- Blood disorders
We are very impressed with this research. It is the first good news we have seen regarding cognitive impairment, memory loss and Alzheimer’s disease in a very long time.
Nevertheless, this is a preliminary study. Since it only lasted a few weeks, it is impossible to know whether the benefits of levetiracetam will persist. Although animal research seems to confirm that the drug should be helpful, larger, longer studies are essential.
There is a problem, though. Levetiracetam is now available generically. That means no drug manufacturer is likely to invest money in a medication that has lost its patent.
The lead investigator, neuroscientist Michela Gallagher, PhD, concludes:
“What we want to discover now, is whether treatment over a longer time will prevent further cognitive decline and delay or stop progression to Alzheimer’s dementia.”
We hope Professor Gallagher will continue her exciting line of research and that other investigators will also join the effort. We are in desperate need of better strategies for preventing and treating this devastating condition. Let’s hope the preliminary findings are confirmed by future research.
The full article can be accessed at this link. Be warned, though. It is written in heavy neuroscientific lingo and is a bit hard to untangle. Nonetheless, we hope other neuroscientists will read this research, keep and open mind and consider testing levetiracetam themselves.
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