White Matter Tract Decline Tracks Cognitive Loss After Frontal Glioma Treatment

Patients with frontal lobe glioma showed parallel declines in cognition and in the microstructural integrity of major white matter tracts across surgery and radiotherapy, and the magnitude of tract change tracked the magnitude of cognitive change, according to a retrospective diffusion tensor imaging study published in BMC Medical Imaging. In 40 patients assessed before surgery, one month after surgery, and six months after the completion of radiotherapy, Montreal Cognitive Assessment (MoCA) scores fell as fractional anisotropy (FA) declined and mean diffusivity (MD) rose in the superior longitudinal fasciculus, the cingulum, and the corpus callosum, with the largest differences at the final assessment. The research team quantified FA and MD in seven major white matter tracts at each of the three visits and assessed cognition with the MoCA.

Longitudinal changes were tested with repeated-measures analysis of variance, and prespecified associations between tract change from the postoperative to the post-radiotherapy assessment and concurrent cognitive change were examined with false discovery rate correction. The retrospective design followed all patients through the same schedule covering the perioperative period and the subsequent multimodal treatment course. The cognitive results showed a stepwise decline across the treatment course.

MoCA total scores averaged 25.34 ± 2.20 before surgery and 25.15 ± 2.47 one month after surgery, then fell to 23.87 ± 2.91 six months after radiotherapy, a longitudinal change that reached statistical significance (P < 0.001). Domain-level analysis identified significant longitudinal changes in visuospatial and executive function and in delayed recall. The imaging data followed a matching course.

The superior longitudinal fasciculus, cingulum, and corpus callosum each showed significant longitudinal FA reductions accompanied by MD increases, and in each of these tracts the largest differences appeared at the six-month post-radiotherapy assessment. Structure-function comparisons from one month after surgery to six months after radiotherapy showed that change in corpus callosum FA correlated with change in MoCA total score (r = 0.57, q < 0.001). Change in superior longitudinal fasciculus FA correlated with change in visuospatial and executive performance (r = 0.41, q = 0.013), and change in cingulum FA correlated with change in delayed recall (r = 0.39, q = 0.013).

Secondary analyses examined whether tract change differed across cognitive-trajectory groups and whether it tracked treatment variables. Corpus callosum FA showed a significant group-by-time interaction after false discovery rate correction, consistent with differences in the longitudinal course of callosal integrity between groups defined by their pattern of cognitive change. In contrast, FA changes in the three tracts showed no significant associations with either extent of resection or total prescribed radiation dose.

The authors interpret the converging patterns as evidence that cognitive dysfunction in frontal lobe glioma may reflect disruption of distributed white matter networks in addition to focal cortical involvement, and they conclude that longitudinal white matter network assessment may hold clinical relevance for monitoring patients through the perioperative and post-radiotherapy phases. These conclusions carry the limits of the design. The study was retrospective and included a single cohort of 40 patients, so the findings describe associations observed in this group rather than effects established in a controlled comparison.

The absence of an association with radiation dose in this cohort does not exclude radiation effects at other doses or time scales. Within those boundaries, the study provides longitudinal, tract-specific evidence that changes in white matter microstructure and changes in cognition proceed together at defined stages of frontal lobe glioma treatment.

Subject of Research: Longitudinal white matter microstructural and cognitive changes in frontal lobe glioma

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

Article References: Chen, J., Wang, Z., Luo, J., Tian, Z., & Huang, C. (2026). Longitudinal cognitive and white matter tract changes in frontal lobe glioma: a retrospective diffusion tensor imaging study. BMC Medical Imaging. https://doi.org/10.1186/s12880-026-02971-3

Image Credits: AI Generated

DOI: 10.1186/s12880-026-02971-3

Keywords: frontal lobe glioma, diffusion tensor imaging, fractional anisotropy, mean diffusivity, white matter tracts, corpus callosum, superior longitudinal fasciculus, cingulum, cognitive dysfunction, Montreal Cognitive Assessment, radiotherapy, neuro-oncology