Smaller hippocampal subfield volumes predict verbal associative memory in pediatric brain tumor survivors

Abstract

The developing hippocampus is highly sensitive to chemotherapy and cranial radiation treatments for pediatric cancers, yet little is known about the effects that cancer treatents have on specific hippocampal subfields. Here, we examined hippocampal subfield volumes in 29 pediatric brain tumor survivors treated with cranial radiation and chemotherapy, and 30 healthy developing children and adolescents. We also examined associations between hippocampal subfield volumes and short-term verbal memory. Hippocampal subfields (Cornus Ammonis (CA) 1, CA2-3, dentate gyrus (DG)-CA4, stratum radiatum-lacunosum-moleculare, and subiculum) were segmented using the Multiple Automatically Generated Templates for Different Brains automated segmentation algorithm. Neuropsychological assessment of short-term verbal associative memory was performed in a subset of brain tumor survivors (N = 11) and typically developing children (N = 16), using the Children's Memory Scale or Wechsler's Memory Scale-third edition. Repeated measures analysis of variance showed that pediatric brain tumor survivors had significantly smaller DG-CA4, CA1, CA2-3, and stratum radiatum-lacunosum-moleculare volumes compared with typically developing children. Verbal memory performance was positively related to DG-CA4, CA1, and stratum radiatum-lacunosum-moleculare volumes in pediatric brain tumor survivors. Unlike the brain tumor survivors, there were no associations between subfield volumes and memory in typically developing children and adolescents. These data suggest that specific subfields of the hippocampus may be vulnerable to brain cancer treatments, and may contribute to impaired episodic memory following brain cancer treatment in childhood.

Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study

“… 27 There are also data suggesting that the hippocampal volume is reduced in survivors of pediatric brain tumors and that this volume reduction is associated with a decline in memory. 28 …”

Neurocognitive Outcomes in Children with Brain Tumors

“…53 Additionally, CRT overlap with the hippocampus further portends a poorer neurocognitive prognosis in survivors, similar to anticipated toxic effects of chemotherapy on the hippocampus. 46,54,55 Proton-based CRT is one modifying factor that continues to undergo investigation as a means to decrease CRT-related neurocognitive injury. Proton CRT has less radiation scatter and ideally treats a more targeted volume with decreased radiation exposure to surrounding healthy tissue.…”

Dose–volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study

“…Notably, memory performance of adult survivors of PBT is related to hippocampal volume but not whole brain or putamen volumes . Findings from a recent study examining associations between hippocampal subfield volumes (cornus ammonis [CA] 1, CA2‐3, dentate gyrus [DG]‐CA4, stratum radiatum–lacunosum–moleculare [SRLM], and subiculum) and verbal short‐term memory revealed smaller DG‐CA4, CA1, CA2‐3, and SRLM volumes in PBT survivors compared to healthy children; and positive correlations between verbal memory and DG‐CA4, CA1, and SRLM volumes …”