Microstructural Alterations of White Matter Associated With Colorectal Cancer-Related Cognitive Impairment

PURPOSE Colorectal cancer survivors exhibit impairments in information processing and working memory with no significantly added effects from adjuvant therapy (PMID: 26527785). Little is known regarding its neural mechanism, which greatly impedes the development of effective therapies. White matter (WM) is an area of interest as it is the predominant tissue that facilitates communication between different brain regions and from which damage could be debilitating. Here, we utilize 7T magnetic resonance diffusion tensor imaging (DTI) to investigate WM integrity and its association with colorectal cancer-related cognitive impairment (CRCI). METHODS 16 subjects were recruited for this ongoing study. These included 7 colorectal cancer survivors (stage I or II, aged 61.8 ± 9.6 years) who had surgery without adjuvant therapy within 6 months, and 9 age/sex/education matched healthy controls (HC, aged 58.1 ± 10.0 years). All subjects had no prior malignancy or history of neurological disorders. Each underwent neuropsychological testing and DTI on a Siemens MAGNETOM Terra 7T scanner within the same day. We then quantitatively compared the WM integrity between survivors and HCs using voxel-wise DTI measures that reflect WM tissue organization including axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA). We also correlated the cognitive test scores with DTI metrics while including the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scores as covariates. RESULTS Compared to HCs, the survivor group performed significantly worse in attention and psychomotor speed on the Trail Making Test (TMT)-A. No significant differences were observed in the BDI or STAI scores. The DTI tract-based spatial statistics found significantly decreased AD and MD in the corpus callosum connecting the two frontal hemispheres (multiple comparison corrected p<0.05). Additionally, the TMT-A scores correlated with mean regional AD, MD, and FA in the genu, body, and forceps minor of the corpus callosum (p<0.05). These results suggest that damage within WM tracts is associated with cognition. CONCLUSION Our ongoing study presents preliminary evidence of alterations and associations between WM microstructural integrity and cognitive functioning in colorectal cancer survivors. Further data collection is underway that will help elucidate the neural mechanism and biological targets needed for treating colorectal CRCI.