Late-onset Temporal Lobe Epilepsy: a phenotypic characterization through fluid biomarkers and clinical data

Introduction Late-onset epilepsy (LOE) is defined by seizure onset after the age of 50 years. The progressive aging of the population and the increase in life expectancy have contributed to a rising incidence of LOE, a trend expected to continue in the coming years. Recent studies have demonstrated a significant association between late-onset temporal lobe epilepsy (LO-TLE) and Alzheimer’s disease (AD), suggesting a possible pathophysiological overlap between the two conditions. The present study aims to further investigate this association and to better characterize the clinical and cognitive profile of patients with LO-TLE. Methods A total of 48 patients with LO-TLE and 32 healthy controls (HC) were enrolled. All participants underwent a comprehensive neuropsychological assessment exploring five cognitive domains: short-term memory, episodic memory, language, attention, and executive functions. In addition, plasma levels of neurodegeneration biomarkers (NfL, Aβ, and tau) were measured in both groups, whereas cerebrospinal fluid (CSF) biomarkers were assessed only in patients with LO-TLE. Results Our findings revealed a relatively widespread but non-uniform cognitive impairment involving multiple cognitive domains in the LO-TLE cohort. The most pronounced deficits were observed in language, executive functions, and global cognition, while significant impairments were also detected in episodic and short-term memory. No significant differences emerged in attention after adjustment for age, sex, and education. Conversely, neurodegeneration biomarkers were comparable between patients and healthy controls. Furthermore, no significant associations were found between cognitive performance and seizure frequency, age at onset, or disease duration Conclusions The observed cognitive impairment appeared to be independent of AD-related neurodegeneration and may instead reflect the effects of epileptogenic activity. Overall, these results support the existence of a distinct cognitive phenotype in LO-TLE and highlight the need for further studies to better characterize its underlying mechanisms.