PATIENTS with Alzheimer’s disease exhibit increased high-frequency oscillations (HFOs), with a differential response to levetiracetam compared to those with and without epileptic activity, new research has shown.
Alzheimer’s disease is associated with an increased risk of epilepsy and cognitive decline. Identifying neurophysiological biomarkers of hyperexcitability could improve early diagnosis and management. High-frequency oscillations (HFOs) are emerging as potential indicators of epileptic activity, but their presence in Alzheimer’s disease has not been fully explored. This study investigated HFOs in patients with epileptic and non-epileptic Alzheimer’s disease, assessing their response to levetiracetam treatment.
Using magnetoencephalography (MEG) recordings from 14 Alzheimer’s patients (six non-epileptic, eight with subclinical epileptic activity) and eight healthy controls, researchers measured HFOs, categorising them into ripples (80–250 Hz) and fast ripples (250–500 Hz). At baseline, both epileptic and non-epileptic Alzheimer’s groups showed a significantly higher rate of HFOs than controls in various brain regions (P < 0.05). Interestingly, non-epileptic Alzheimer’s patients had more ripples in left-frontal, left-temporal, and cerebral fissure regions, as well as more fast ripples in the left-frontal region than those with epilepsy (P < 0.05). Levetiracetam treatment reduced ripples in frontal, occipital, and cerebral fissure regions in the epileptic group, whereas it increased ripples and fast ripples in parietal and central regions in non-epileptic patients (P < 0.05). Additionally, hemispheric asymmetry was observed in epileptic Alzheimer’s patients, with the right temporal and occipital regions exhibiting more HFOs.
These findings highlight HFOs as potential biomarkers for hyperexcitability in Alzheimer’s disease, with their asymmetry possibly indicating pathological relevance. Clinically, levetiracetam may offer targeted benefits for epileptic Alzheimer’s patients by reducing hyperexcitability, but its effects on non-epileptic patients require further evaluation. Future research should explore whether HFO modulation can improve cognitive outcomes and refine treatment strategies, optimising care for Alzheimer’s patients at risk of epilepsy.
Katrina Thornber, EMJ
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 Communications. 2025;DOI:10.1093/braincomms/fcaf041.
