Authors :
Presenting Author: Aswathy Ammothumkandy, PhD – University of Southern California
Luis Corona, MS – University of Southern California
Jonathan Russin, MD – University of Southern California
Charles Liu, MD, PhD – University of Southern California
Jason Smith, PhD – Medical University of South Carolina
Michael Bonaguidi, PhD – University of Southern California
Rationale:
Progressive cognitive decline frequently occurs in epilepsy patients and is amplified by age. However, the cellular mechanisms underlying this age-associated vulnerability are poorly understood. Our previous research in Mesial Temporal Lobe Epilepsy (MTLE) patients identified pathological stellar Dcx+ immature astroglia in epileptic, but not healthy, hippocampus. In this study we investigated whether these pathological immature astroglia correspond with age-related cognitive decline in human MTLE patients.
Methods:
In this study, we combined histology data with pre-surgical 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). Cognitive functioning was evaluated pre-surgically using the Neuropsychological Screening Battery for Hispanics (NeSBHIS). We first identified which cognitive domains were affected by age. 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 astroglia were quantified by performing histology in surgically resected hippocampal tissue (N = 19).
Results:
We observed a strong decline in intelligence, visuospatial reconstruction, and visual memory with age. An increase in Dcx+ immature astroglia positively correlated with age and negatively correlated with intelligence scores.Conclusions:
These findings reveal a new interplay among aging, intellectual decline, and immature astroglia prevalence in epilepsy patients. Our study suggests immature astroglial are maladaptive to human intelligence and reasoning, and provide a cellular target to ameliorate age-associated cognitive decline in patients with epilepsy.
Funding: American Epilepsy Society, California Institute for Regenerative Medicine, Cure Epilepsy