Lateralization of interictal epileptiform discharges differently impacts cognitive performance and behavior in...

Late-onset epilepsy of unknown aetiology (LOEU) is increasingly recognized as a multifactorial condition potentially linked to preclinical neurodegeneration. Despite its clinical relevance, the impact of lateralized interictal epileptiform discharges (IEDs) on cognitive and behavioral phenotypes remains poorly understood.

We conducted an observational cross-sectional study of 62 LOEU patients (66.1 ± 7.3 years). All participants underwent neurological examination, electroencephalography, and a neuropsychological battery. Subjective sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth Sleepiness Scale), depressive symptoms (Beck Depression Inventory-II), and quality of life (Quality of Life in Epilepsy Inventory-31) were also assessed. Patients were stratified based on IED lateralization (Left vs. Right).

IEDs were left-lateralized in 61.3% (n = 38) and right-lateralized in 38.7% (n = 24). A significant difference emerged only for delayed verbal recall (RAVLT-D), with right-lateralized patients performing worse (p = 0.043). No differences were found in other cognitive domains, sleep, mood, or quality of life.

While right-sided IEDs were associated with lower RAVLT-D performance, this represents a nominally significant finding in the context of multiple domains tested without correction for multiple comparisons. These results may suggest a distributed pattern of cognitive vulnerability, possibly reflecting network dysfunction or inefficient interhemispheric integration. Findings should be interpreted with caution and considered exploratory. Given that RAVLT-D is a marker of hippocampal dysfunction and early neurodegeneration, these results support longitudinal monitoring to identify LOEU patients at higher risk of dementia, regardless of focal lateralization.