Abstract
Introduction: Despite the fact that epilepsy has been associated with cognitive decline, neuropsychological, neurobiological, and neurophysiological features in patients with late-onset epilepsy of unknown etiology (LOEU) are still unknown. This cross-sectional study aims to investigate the neuropsychological profile, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), and resting-state quantitative electroencephalographic (qEEG) cortical rhythms in LOEU patients with mild cognitive impairment (LOEU-MCI) and with normal cognition (LOEU-CN), compared to non-epileptic MCI (NE-MCI) and cognitively normal (CN) controls.Methods: Consecutive patients in two clinical Units diagnosed with LOEU-CN (19), LOEU-MCI (27), and NE-MCI (21) were enrolled, and compared to age and sex-matched cognitively normal subjects CN (11). Patients underwent standardized comprehensive neuropsychological evaluation and CSF core AD biomarkers assessment (i.e., CSF Aβ42, phospho-tau and total tau, classified through A/T/(N) system). Recordings of resting-state eyes-closed electroencephalographic (EEG) rhythms were collected and cortical source estimation of delta (<4 Hz) to gamma (>30 Hz) bands with exact Low Resolution Electromagnetic Tomography (eLORETA) was performed.Results: Most LOEU patients had an MCI status at seizure onset (59%). Patients with LOEU-MCI performed significantly worse on measures of global cognition, visuo-spatial abilities, and executive functions compared to NE-MCI patients (p < 0.05). Regarding MCI subtypes, multiple-domain MCI was 3-fold more frequent in LOEU-MCI than in NE-MCI patients (OR 3.14, 95%CI 0.93–10.58, p = 0.06). CSF Aβ42 levels were lower in the LOEU-MCI compared with the LOEU-CN group. Finally, parietal and occipital sources of alpha (8–12 Hz) rhythms were less active in the LOEU-MCI than in the NE-MCI and CN groups, while the opposite was true for frontal and temporal cortical delta sources.Discussion: MCI status was relatively frequent in LOEU patients, involved multiple cognitive domains, and might have been driven by amyloidosis according to CSF biomarkers. LOEU-MCI status was associated with abnormalities in cortical sources of EEG rhythms related to quiet vigilance. Future longitudinal studies should cross-validate our findings and test the predictive value of CSF and EEG variables.
Highlights
Despite the fact that epilepsy has been associated with cognitive decline, neuropsychological, neurobiological, and neurophysiological features in patients with late-onset epilepsy of unknown etiology (LOEU) are still unknown
late onset epilepsy of unknown etiology (LOEU)-MCI patients were older at seizure onset (69.2 vs. 65.1 years) and had lower education (8.3 vs. 11.1) compared to LOEU-cognitively normal (CN) patients (p < 0.05)
Despite the higher risk of developing cognitive impairment and dementia in subjects with epilepsy, we still lack data on cognitive performance and tools to stratify the risk of decline in LOEU [4, 14, 15, 17, 35]
Summary
Despite the fact that epilepsy has been associated with cognitive decline, neuropsychological, neurobiological, and neurophysiological features in patients with late-onset epilepsy of unknown etiology (LOEU) are still unknown. Only isolated reports are available, yet they do not providing the prevalence and characterization of cognitive impairment in people who have received a LOE diagnosis [4, 14,15,16]. Such issues, though under-investigated, might offer critical insights to define the processes shared by epileptogenesis and neurodegeneration. An intertwining that becomes critical for patients with late onset epilepsy of unknown etiology (LOEU), that make up 20% of LOE, and among which extensive investigations yield no vascular, structural, or systemic etiology [15, 17]
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