Levetiracetam may be viable as biomarker for Alzheimer’s disease
Key takeaways:
- Levetiracetam decreased high-frequency oscillations in patients with AD and epilepsy, and increased them in non-epileptic patients with AD.
- The right temporal and occipital lobes had more high-frequency oscillations than the left.
The effect of levetiracetam, an antiseizure therapy, on high-frequency oscillation in patients with Alzheimer’s disease as well as epilepsy may prove its viability as a biomarker of disease pathology, according to data.
“The current study addresses unmet needs in the early diagnosis, risk stratification and therapeutic management of Alzheimer’s patients with epileptic activity,” Keith Vossel, MD, study co-author, neurologist and director of the Katherine and Benjamin Kagan Alzheimer’s Disease Treatment Development Program in the David Geffen School of Medicine at UCLA, told Healio. “While previous studies linked network alterations to epileptic activity, this is the first to show normalization of epilepsy-associated brain activity with antiseizure treatment in Alzheimer’s disease.”
Although prior research suggests that high-frequency oscillations may be potential biomarkers of hyperexcitability and epileptic activity, these have not been identified in AD, Vossel and colleagues wrote in Brain Communications.
The researchers investigated high-frequency oscillations through magnetoencephalography (MEEG) recordings in patients with AD with and without epileptic activity in a randomized, double-blind, phase 2a clinical trial that examined the efficacy of levetiracetam to improve cognitive functions.
They analyzed 10-minute MEEG recordings of 14 individuals with AD (non-epileptic AD,
n = 6; epileptic AD, n = 8) as well as eight control subjects during both wakefulness and rest with a pair of software scripts: Delphos and one custom-made to detect high-frequency oscillations.
In between the MEEG readings, participants were administered 125 mg levetiracetam or placebo twice per day for 4 weeks, followed by a 4-week washout period ahead of switching between levetiracetam and placebo phases for each enrollee. Each participant given levetiracetam had four MEEG visits with controls logging only one such visit.
High-frequency oscillations taken from MEEG were categorized into ripples (80 Hz to 250 Hz) and fast ripples (250 Hz to 500 Hz).
According to the results, both patients with epileptic AD and non-epileptic AD recorded higher rates of ripples and fast ripples compared with controls in several left/right hemispheric sensor regions.
Compared with patients with epileptic AD, patients with non-epileptic AD logged a higher rate of ripples in left-frontal, left-temporal and cerebral fissure regions as well as higher rate of fast ripples in left-frontal regions.
The researchers further found that levetiracetam decreased ripples in bilateral-frontal, bilateral-occipital regions and cerebral fissure in the epileptic cohort, while levetiracetam increased both ripples and fast ripples in right central and left parietal regions, as well as ripples in the right parietal region for patients with non-epileptic AD.
Data additionally showed that hemisphere asymmetry in epileptic type, with right temporal/occipital having more high-frequency oscillations than their counterpart region.
“By recognizing high-frequency oscillations (HFOs), particularly asymmetric HFOs, as a biomarker of epileptic activity and demonstrating the therapeutic potential of levetiracetam, these findings lay the foundation for more personalized, effective interventions in Alzheimer’s disease management,” Vossel told Healio.
Reference:
Brain rhythms can predict seizure risk of Alzheimer’s disease patients, study finds. https://www.uclahealth.org/news/release/brain-rhythms-can-predict-seizure-risk-alzheimers-disease. Published Feb. 13, 2025. Accessed Feb. 14, 2025.