Positive correlation between cognition and inflammation in the cerebral cortex of patients with mesial temporal lobe epilepsy

Cognitive impairments are commonly observed in individuals with mesial temporal lobe epilepsy (mTLE), yet the underlying mechanisms remain poorly elucidated. This study investigates the potential relationship between neuroinflammation as determined using radioligand binding to markers of neuroinflammation and cognitive dysfunction in this patient population. Quantitative autoradiography was performed using the radioligands [123I]CLINDE (for 18 kDa translocator protein (TSPO)) and [3H]JNJ-64413739 (for P2X purinoceptor 7 receptor (P2X7R)) on temporal neocortical specimens removed neurosurgically from 17 patients with drug-resistant mTLE (41.2 % male; mean age = 41.2 ± 11.4 years). Preoperative cognitive function was assessed using the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV), and Pearson's correlation analyses were conducted to examine associations between radioligand binding and cognitive scores, with subgroup analyses based on the laterality of the epileptic focus. Multiple regression analyses were employed to control for potential confounders, including seizure frequency, epilepsy duration, and lateralization. Significant associations emerged exclusively in patients with left temporal lobe epilepsy. In this subgroup, [123I]CLINDE binding showed a positive correlation with the Verbal Comprehension Index (VCI) (p = 0.037) and the Processing Speed Index (PSI) (p = 0.011). Additionally, [3H]JNJ-64413739 binding was significantly correlated with the Working Memory Index (WMI) (p = 0.029). Sensitivity analyses confirmed a robust association between [123I]CLINDE binding and VCI score (p = 0.002, β = 0.19). These findings demonstrate a positive correlation between TSPO expression and cognitive function in patients with drug-resistant mTLE, and the results contribute to a growing body of evidence linking neuroinflammatory processes to cognitive outcomes in epilepsy.