IMPACTO SOBRE LA COGNICIÓN DE LA EPILEPSIA EN ADULTOS

Abstract

Introduction: patients with temporal lobe epilepsy (TLE) present with multidomain cognitive impairment, predominantly affecting memory, which progresses in parallel with the disease and has a significant impact on their quality of life. Furthermore, they have an increased risk of developing dementia compared to the general population. Given that currently epilepsy treatment is focused almost exclusively on seizure control, the identification of biomarkers that allow early detection of TLE patients at higher risk of cognitive decline is crucial, as it would enable mor specific patient monitoring, and potentially open new lines of research aimed at developing targeted disease-specific treatments. _x000D_ _x000D_ Objectives: to determine the presence of biomarkers associated with neuronal damage and cognitive impairment in adult patients with drug-resistant TLE, by examining cerebrospinal fluid (CSF) Aβ1-42 and p181-tau levels, cerebral Aβ deposits on positron emission tomography (Aβ PET) and baseline cerebral activity assessed by quantitative electroencephalography (qEEG), and correlating these findings with cognitive performance._x000D_ _x000D_ Methods: we conducted two cross-sectional studies including adult patients with drug-resistant TLE who were 25–55 years old. In the first study, each participant underwent 18F- flutemetamol PET, determination of CSF Aβ1-42, p181-tau, and total tau, as well as a comprehensive neuropsychological assessment. In the second study, which also included age and sex-matched controls, we analyzed qEEG samples using the fast Fourier transform approach. Power spectral density (PSD) was calculated for four frequency bands: delta (1–3.9Hz), theta (4–7.9Hz), alpha (8–12.9Hz), and beta (13–18Hz)._x000D_ _x000D_ Results: in our initial sample of 30 patients, high uptake on Aβ PET was observed in both mesial temporal regions (ipsilateral: SUVR z-score= 0.90, 95% confidence interval [CI] = 0.60–1.20; contralateral: SUVR z-score= 0.92, 95% CI = 0.57–1.27; p <0.001), and in the ipsilateral anterior cingulate (SUVR z-score = 0.27, 95% CI = 0.04–.49, p = 0.020), which was significantly higher compared to SUVR z-scores in all the remaining regions. Seven patients (23%) had low Aβ1-42 levels, and two (7%) had elevated p181-tau levels in CSF. Higher p181-tau levels correlated with poorer verbal fluency (R = −.427, p = .044). When comparing baseline qEEG activity to controls, TLE patients showed increased ipsilateral PSD for the theta (p = 0.045), alpha (p = 0.023) and beta (p = 0.029) bands in the anterior region, and for the delta band in the posterior region (p = 0.03). Additionally, the alpha/theta ratio (ATR) was lower in the posterior quadrant of the epileptogenic hemisphere (p = 0.013). TLE patients with amnestic cognitive impairment exhibited higher PSD across most frequency bands (p < 0.005), and impaired verbal memory and executive function were associated with increased PSD._x000D_ _x000D_ Conclusions: our study identified increased Aβ load in mesial temporal regions and ipsilateral anterior cingulate, along with abnormal CSF Aβ1-42 levels in patients with drug-resistant TLE. Higher pTau levels were associated with impaired verbal fluency. Analysis of baseline qEEG revealed increased PSD in all frequency bands in the epileptogenic hemisphere, particularly in those patients with amnestic cognitive impairment. This finding was associated with impaired verbal memory and executive functioning. These findings offer insights into potential biomarkers of neuronal damage associated with epilepsy, however, further long-term follow-up studies are warranted to validate these observations.

Date of Award	31 Oct 2025
Original language	Spanish
Awarding Institution	Universitat Autònoma de Barcelona (UAB)
Supervisor	Manuel Toledo Argany (Director) & Elena Fonseca Hernández (Director)