B – 8 Age-related intellectual decline corresponds with immature astroglia prevalence in patients with epilepsy.

Abstract Objective Progressive cognitive decline frequently occurs in epilepsy patients and amplifies with age. The cellular mechanisms underlying this age-associated vulnerability remain poorly understood. Previous research in Mesial Temporal Lobe Epilepsy (MTLE) patients identified pathological stellar Dcx+ immature astroglia in epileptic, but not healthy, hippocampus. The present study combined histology data with presurgical neuropsychology tests to assess 1) age-associated cognitive decline in MTLE patients (N = 40), 2) age-related changes in Dcx+ immature astroglia (N = 29), and 3) the association between Dcx+ immature astroglia and cognitive decline (N = 19). Method Patients with MTLE underwent presurgical neuropsychological evaluation using the Neuropsychological Screening Battery for Hispanics (NeSBHIS). First, cognitive domains from the NeSBHIS that were affected by age were identified. Education-normalized NeSBHIS Z scores were analyzed from MTLE patients (N = 40), with average age (M = 39.88 years; SD = 11.56), Disease duration (M = 26.74 years; SD = 14.05), and reported years of education (M = 7.9 years; SD = 3.51). Dcx+ Immature neurons were quantified by performing histology in surgically resected hippocampal tissue (N = 19). Results Spearman’s correlations revealed significant declines in intelligence, visuospatial reconstruction and memory with age. Increased Dcx+ immature astroglia in the molecular layer (ML) positively correlated with age, while negatively correlating with intelligence scores. See Figure. Conclusion Results reveal an interplay among aging, intellectual decline and immature astroglia prevalence in patients with MTLE. Immature astroglia may be maladaptive to human intelligence/reasoning and are a potential therapeutic, cellular target to mitigate age-associated cognitive decline in aging patients with MTLE.