HIGH-frequency oscillations (HFOs) as potential biomarkers in Alzheimer’s disease (AD), have been highlighted in a new study, offering insight into how epilepsy affects neurodegeneration. The study also revealed that the anti-epileptic drug levetiracetam produces contrasting effects on brain activity in patients with AD with and without epilepsy.
HFOs, which include ripples (80–250 Hz) and fast ripples (250–500 Hz), are emerging as indicators of brain hyperexcitability and epileptic activity. Until now, their role in Alzheimer’s disease remained unclear. Researchers conducted magnetoencephalography (MEG) recordings in 14 Alzheimer’s patients, eight with subclinical epilepsy and six without, alongside eight healthy controls. The findings showed that both epileptic and non-epileptic Alzheimer’s patients exhibited significantly higher levels of HFOs compared to controls, particularly in key brain regions.
Notably, non-epileptic patients with AD exhibited even greater HFO activity than their epileptic counterparts, particularly in the left-frontal, left-temporal, and cerebral fissure regions. This suggests that HFOs may serve as early biomarkers of neurodegeneration in Alzheimer’s, beyond their association with epilepsy.
The study also evaluated the effects of levetiracetam, administered at 125 mg twice daily over a 4-week period. In epileptic patients with AD, levetiracetam reduced HFOs in several brain regions, supporting its potential as a treatment for network hyperexcitability. However, in non-epileptic patients with AD, the drug unexpectedly increased HFOs in specific brain areas, raising questions about its impact on cognitive function in this subgroup.
These findings reinforce the role of HFOs as a biomarker of hyperexcitability in Alzheimer’s disease and highlight the need for personalized approaches in treating neurodegeneration with anti-epileptic drugs.
Reference: Vishnu Shandilya MC et al. High-frequency oscillations in epileptic and non-epileptic Alzheimer’s disease patients and the differential effect of levetiracetam on the oscillations. Brain Commun. 2025;7(1):fcaf041.
Anaya Malik | AMJ
