Atrophy of Entorhinal Cortex After Radiation Therapy Associated With Memory Decline

Abstract

Brain radiation therapy (RT) is associated with impaired memory, which may be mediated in part by damage to cerebral cortex. The entorhinal cortex is the primary input source for the hippocampus and is important for memory formation. This structure has been shown to be selectively vulnerable to RT dose-dependent atrophy. We hypothesized that post-RT atrophy of the entorhinal cortex on MRI would be associated with post-RT memory impairment. We measured change in thickness of the entorhinal cortex in primary brain tumor patients participating in a prospective clinical trial of imaging and neurocognitive changes after partial brain RT. Study patients underwent neurocognitive testing and high-resolution 3-D volumetric MRI (T1-weighted IR-SPGR and T2 FLAIR) prior to and 6 months after RT. A preliminary analysis revealed Total Recall on the Brief Visuospatial Memory Test (BVMT-R) to be sensitive to changes in memory performance after RT, so this measure was chosen for the present analysis. Imaging and BVMT-R data were available at both time points for 18 patients. MRI data were corrected for distortion. Automated software and visual verification were used to segment the cerebral cortex and measure mean thickness of the entorhinal region bilaterally at each time point for each patient. Post-treatment changes were manually censored from analysis. A reliable change index, accounting for serial testing practice effects, was calculated for each subject’s memory performance across time. Average change in left and right entorhinal thickness was tested for association with change in memory performance via simple linear regression. Statistical significance was set at α = 0.05 for two-sided tests. Most (72%) patients had low grade or benign tumors, and median prescription dose was 54 Gy (range 50.4-60 Gy). After censoring post-treatment changes, thickness was measured for 14 left and 17 right entorhinal regions. Atrophy in the left entorhinal cortex at 6 months post-RT was associated with decline in visuospatial memory (3 point decline per mm atrophy, P = 0.01). The analogous test for the right entorhinal cortex was not significant (P = 0.31). Atrophy in the left entorhinal cortex 6 months after RT was associated with decline in visuospatial memory performance. These data confirm the role of the entorhinal cortex in memory formation and suggest that this region may be critical to RT-associated memory decline.