An age-related decline in human fluid intelligence corresponds with immature astroglia prevalence

Age-related cognitive decline remains a daunting health challenge, and targeting neuronal cells alone has been insufficient to halt its progression. Astroglia are emerging as key players in cognitive function and dysfunction, yet their relevance to age-associated cognitive decline in humans remains unclear. Epilepsy patients undergo age-amplified progressive cognitive decline. Our prior research in Mesial Temporal Lobe Epilepsy (MTLE) patients identified pathological stellar Dcx + immature astroglia in epileptic, but not healthy hippocampus. 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). We observed a strong decline in fluid intelligence, visuospatial reconstruction, and memory with age. An increase in Dcx + immature astroglia positively correlated with age, whereas negatively associated with nonverbal abstract reasoning and fluid intelligence as measured by the Raven's Progressive Matrices test. These findings reveal an interplay among aging, fluid intelligence decline, and immature astroglia prevalence in epilepsy patients. Our study suggests immature astroglia represent a new cellular target to consider for altering age-associated cognitive decline.