A Kaleidoscope of Cognitive Vulnerability in Temporal Lobe Epilepsy

Cognitive Phenotypes in Patients With Drug-Resistant Temporal Lobe Epilepsy: Relationships With Cortisol and Affectivity Cano-López I, Catalán-Aguilar J, Lozano-García A, Hidalgo V, Hampel KG, Tormos-Pons P, Salvador A, Villanueva V, González-Bono E. Clin Neuropsychol . 2025;39(2):400-423. Epub 2024 Jul 4. PMID: 38965831. Objective: Drug-resistant temporal lobe epilepsy (TLE) is a neurological disorder characterized by cognitive deficits. This study examined whether patients with TLE and different cognitive phenotypes differ in cortisol levels and affectivity while controlling for demographic and clinical variables. Methods: In this cross-sectional study, 79 adults with TLE underwent neuropsychological evaluation in which memory, language, attention/processing speed, executive function, and affectivity were assessed. Six saliva samples were collected in the afternoon to examine the ability of the hypothalamic-pituitary-adrenal (HPA) axis to descend according to the circadian rhythm (C1 to C6). The cortisol area under the curve concerning ground (AUCg) was computed to examine global cortisol secretion. Results: Three cognitive phenotypes were identified: memory impairment, generalized impairment, and no impairment. The memory-impairment phenotype showed higher cortisol levels at C4, C5, and C6 than the other groups ( p  = 0.03, η 2  = 0.06), higher cortisol AUCg than the generalized-impairment phenotype ( p  = 0.004, η 2  = 0.14), and a significant reduction in positive affectivity after the evaluation ( p  = 0.026, η 2  = 0.11). Higher cortisol AUCg and reductions in positive affectivity were significant predictors of the memory-impairment phenotype ( p  < 0.001; Cox and Snell R 2  = 0.47). Conclusions: Patients with memory impairment had a slower decline in cortisol levels in the afternoon, which could be interpreted as an inability of the HPA axis to inhibit itself. Thus, chronic stress may influence hippocampus-dependent cognitive function more than other cognitive functions in patients with TLE.