Entorhinal Cortical Volume is Associated With Verbal and Visuospatial Memory Performance in Primary Brain Tumor Patients

PURPOSE/OBJECTIVE(S) The entorhinal cortex in the medial temporal lobe is a critical part of the hippocampal memory system, crucial for memory formation and consolidation. Studies show the entorhinal cortex is particularly vulnerable to dose-dependent atrophy. We examined the association between entorhinal cortical volume and longitudinal verbal and visuospatial memory function in a prospective cohort of primary brain tumor patients. MATERIALS/METHODS Primary brain tumor patients (n = 50) undergoing fractionated brain RT were enrolled in a prospective trial and underwent volumetric brain MRI and verbal and visuospatial memory assessments (Hopkins Verbal Learning Test Total/Delayed [HVLT-Total, HVLT-Delayed] and Brief Visuospatial Memory Test Total/Delayed [BVMT-Total, BVMT-Delayed]) at baseline and 3-, 6-, and 12-months post-RT. Reliable change indices (RCI-PE) measured change in scores, adjusting for practice effects, and one-sample t-tests evaluated for significance. Left- and right-sided entorhinal cortices were autosegmented; tumor, surgical bed, and edema were censored to avoid confounding. Entorhinal cortical volume was measured, and linear mixed-effects modeling assessed entorhinal cortical volume as a longitudinal predictor of memory scores after controlling for time and subject-specific effects. P-values were corrected for multiple comparisons. RESULTS Among the cohort, median patient age was 50 years, 50% had gliomas, and 52% had left sided tumors. Median number of years of formal education was 15 (range 10-20). HVLT-Total/Delayed and BVMT-Total scores declined from baseline to 12 months post-RT (HVLT-Total RCI = -0.74, P = 0.032; HVLT-Delayed RCI = -1.39, P < 0001; BVMT-Total RCI = -0.64, P = 0.034). Patients with higher education attainment had less change in delayed verbal memory (baseline to 12 months, P = 0.01). Mean doses to right and left entorhinal cortices were not significantly different (P = 0.99). Higher radiation dose to the right entorhinal cortex was significantly associated with volume atrophy (P < 0.0001). Left entorhinal cortical atrophy was associated with worse total and delayed verbal memory performance (HVLT-Total P = 0.002, HVLT-Delayed P = 0.023). CONCLUSION Higher educational attainment was associated with less memory decline among primary brain tumor patients after RT. The right entorhinal cortex displayed significant radiation dose-dependent atrophy. Left entorhinal cortical atrophy predicted worse total and delayed verbal memory performance after RT. Beyond the hippocampus, the entorhinal cortex is also a critically important memory structure. HYPOTHESIS Atrophy of the entorhinal cortex is associated with worse visuospatial and verbal memory in the first year after brain radiotherapy.