According to research published in the September 27th edition of JAMA Neurology, an affordable anti-seizure medicine significantly improves learning, memory, and other cognitive abilities in Alzheimer’s patients with epileptic activity in their brains.
“This is a drug that’s used for epilepsy,” says Keith Vossel, MD, MSc, director of the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, and the principal investigator on the clinical trial. “We used it in this study for Alzheimer’s patients who had evidence of silent epileptic activity, which is seizure-like brain activity without the associated physical convulsions.”
Alzheimer’s disease (AD) is the most common cause of dementia across the world. Short-term memory loss, a deterioration in problem-solving, word-finding issues, and difficulty with spatial navigation are all early indications. An estimated 10-22 percent of Alzheimer’s patients experience seizures, with another 22-54 percent exhibiting quiet epileptic activity.
There’s a subtype of Alzheimer’s disease, consider it an epileptic variant, that’s quite common, occurring in approximately 60% of patients. Patients with this form of Alzheimer’s disease show symptomatic improvement with levetiracetam.Dr. Vossel
In previous investigations, Dr. Vossel found that individuals who have quiet epileptic activity in their brains had a faster loss in cognitive performance. The researchers selected to test levetiracetam, an anti-seizure medicine that was licensed by the FDA in 1999 and had previously shown to be effective in animal models of Alzheimer’s disease.
Levetiracetam is now available as a generic and costs roughly $70 per year. The experiment employed a dosage of 125 mg twice a day, which is far lower than a normal epilepsy treatment.
An electroencephalogram (EEG) was used to monitor 54 individuals with moderate Alzheimer’s symptoms overnight, as well as an hour-long magnetoencephalogram (MEG) to capture magnetic waves created by electrical activity, to screen for silent epileptic activity.
“MEG can pick up epileptic activity that EEGs miss because it’s looking at a different population of brain cells,” Dr. Vossel explained.
Only 34 of the patients who were assessed for the research were qualified to participate, with approximately 40% of them exhibiting epileptic activity and the rest having none (patients on anti-seizure medications due to preexisting seizure disorders were excluded prior to screening).
After that, the patients were placed into two groups, with one getting placebo for four weeks, then no medicine for four weeks, and finally a 125 mg dosage of levetiracetam twice daily for four weeks.
In the second group, the identical treatments were given in the opposite sequence. The intervention was evaluated on all participants using a crossover design, which meant neither the patients nor the researchers knew whether the patient was taking the real medicine on any given week.
During the trial, the researchers assessed the patients’ problem-solving, reasoning, memory, and navigation capabilities. Participants learned to negotiate a street route through a virtual city using a driving simulator on a computer display, for example.
The patients treated with levetiracetam exhibited signs of improvement in cognitive function, but when the patients were divided into those with quiet epileptic activity and those without, the patients with silent epileptic activity showed a definite benefit from the medicine.
“There were very clear differences between the groups,” Dr. Vossel says. “There’s a subtype of Alzheimer’s disease, consider it an epileptic variant, that’s quite common, occurring in approximately 60% of patients. Patients with this form of Alzheimer’s disease show symptomatic improvement with levetiracetam.”
Because doctors seldom screen for silent seizures when diagnosing Alzheimer’s disease, the findings of this study may urge them to evaluate if a patient is having epileptic activity.
“There are some clinical features that indicate Alzheimer’s patients are more likely to be having silent epileptic activity,” he says. “The main one is being under the age of 65 when symptoms begin.” In fact, he says, the drug also appeared to benefit younger patients even if they didn’t have detectable epileptic activity.
Patients in the trial were already using FDA-approved Alzheimer’s drugs, and the results show that levetiracetam improves cognitive function more effectively than existing therapies alone. Future research is needed to see if using the medicine long-term can help delay disease development.
“This study was intended to look for cognitive improvement during a short course of treatment,” Dr. Vossel says. “There are other studies that are ongoing to see if the drug can help slow the disease course over longer periods,” adding that future studies at UCLA will focus on recruiting a more diverse study population and testing other anti-seizure medications.
While at the University of California, San Francisco, Dr. Vossel started the research in 2014 and enrolled patients at both UCSF and the University of Minnesota. Grants from the Alzheimer’s Association, the National Institutes of Health, and various private donor sources helped fund the study.
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