PurposeThe pleiotropic effect of gliomas on the development of cognitive disorders and structural brain changes has garnered increasing interest in recent years. While it is widely accepted that multimodal therapies for brain cancer can foster cognitive impairment, the direct effect of gliomas on critical cognitive areas before anti-tumor therapies is still controversial. In this study, we focused on the effect of IDH1 wild-type glioblastoma on the human hippocampus volume.MethodsWe carried out a case-control study using voxel-based morphometry assessment, analyzed with the Computational Anatomy Toolbox software. Glioblastoma diagnosis was performed according to the latest 2021 WHO classification. Due to stringent inclusion criteria, 15 patients affected by IDH1 wild type glioblastoma were included and compared to 19 age-matched controls.ResultsWe observed a statistically significant increase in the absolute mean hippocampal volume (p = 0.017), as well as in the ipsilateral (compared to the lesion, p = 0.027) and the contralateral hippocampal volumes (p = 0.014) in the group of patients. When the data were normalized per total intracranial volume, we confirmed a statistically significant increase only in the contralateral hippocampal volume (p = 0.042).ConclusionsTo the best of our knowledge, this is the first study to explore hippocampal volumetric changes in a cohort of adult patients affected by IDH1 wild-type glioblastoma, according to the latest WHO classification. We demonstrated an adaptive volumetric response of the hippocampus, which was more pronounced on the side contralateral to the lesion, suggesting substantial integrity and resilience of the medial temporal structures before the initiation of multimodal treatments.