Alterations in white matter fiber in Parkinson disease across different cognitive stages

Cognitive impairment in Parkinson disease (PD) leads to substantial disability. Unlike external manifestations such as tremor, the decay of cognitive function is often an underlying process, and its neuroanatomic substrates are not yet fully elucidated. Knowledge regarding cognitive-related alterations in white matter (WM) pathways helps us understand the mechanisms of cognitive decline in patients with PD. Previous voxel-based analyses with Diffusion tensor imaging (DTI) metrics, such as fractional anisotropy (FA) and mean diffusivity (MD) have uncovered white matter differences in groupwise, but the conclusions were inconsistent. That was partially due to white matter fibers that are known to affect cognition, such as the corpus callosum (CC) and superior longitudinal fasciculus that cross in voxel, and are hard to interpreted by the abovementioned metrics. Furthermore, cognitive decay is a continuous process, it is difficult to reflect the continuous changes of white matter fibers between groups comparison. In the present work, we chose the constrained spherical deconvolution (CSD) and the fixel model, which avoided the effect of crossing fibers. To compare the white matter fiber in different cognitive stages of patients with PD, the results found that the CC, the cingulum bundle (CB), and the corticospinal tract (CST) showed the same trend in the decline of cognitive function, and this change may lead to the impairment of cognitive function. Our findings can help physicians determine the cognitive stage of PD from the perspective of white matter fiber and provide a reference for clinical trials and predictions.