Longitudinal cognitive and white matter tract changes in frontal lobe glioma: a retrospective diffusion tensor imaging study

Cognitive dysfunction in frontal lobe glioma may reflect disruption of distributed white matter networks in addition to focal cortical involvement. Longitudinal evidence linking tract-specific microstructural changes to concurrent cognitive changes across the perioperative and subsequent multimodal treatment course remains limited. Forty patients with frontal lobe glioma were evaluated before surgery (T0), 1 month after surgery (T1), and 6 months after completion of radiotherapy (T2). Cognition was assessed using the Montreal Cognitive Assessment (MoCA). Fractional anisotropy (FA) and mean diffusivity (MD) were quantified in seven major white matter tracts. Longitudinal changes were tested using repeated-measures analysis of variance. Prespecified T1-to-T2 structure–function associations were examined with false discovery rate correction. Secondary analyses assessed cognitive-trajectory groups and associations with extent of resection and total prescribed radiation dose. MoCA total scores decreased from 25.34 ± 2.20 at T0 and 25.15 ± 2.47 at T1 to 23.87 ± 2.91 at T2 ( P < 0.001), with significant longitudinal changes in visuospatial/executive function and delayed recall. The superior longitudinal fasciculus (SLF), cingulum (Cg), and corpus callosum (CC) showed significant longitudinal FA reductions and MD increases, with the largest differences at T2. From T1 to T2, changes in CC FA correlated with MoCA total-score change ( r = 0.57, q < 0.001), SLF FA with visuospatial/executive change ( r = 0.41, q = 0.013), and Cg FA with delayed-recall change ( r = 0.39, q = 0.013). CC FA showed a significant group-by-time interaction after false discovery rate correction. No significant associations were found between T1-to-T2 FA changes in the SLF, Cg, or CC and either extent of resection or total prescribed radiation dose. Frontal lobe glioma patients showed longitudinal cognitive and white matter microstructural changes across the perioperative and subsequent multimodal treatment course. Concurrent changes in the CC, SLF, and Cg were associated with changes in global cognition, visuospatial/executive function, and delayed recall, respectively, supporting the clinical relevance of longitudinal white matter network assessment.