Abstract
Patients with Wilson’s disease (WD) suffer from prospective memory (PM) impairment, and some of patients develop cognitive impairment. However, very little is known about how brain structure and function changes effect PM in WD. Here, we employed multimodal neuroimaging data acquired from 22 WD patients and 26 healthy controls (HC) who underwent three-dimensional T1-weighted, diffusion tensor imaging (DTI), and resting state functional magnetic resonance imaging (RS-fMRI). We investigated gray matter (GM) volumes with voxel-based morphometry, DTI metrics using the fiber tractography method, and RS-fMRI using the seed-based functional connectivity method. Compared with HC, WD patients showed GM volume reductions in the basal ganglia (BG) and occipital fusiform gyrus, as well as volume increase in the visual association cortex. Moreover, whiter matter (WM) tracks of WD were widely impaired in association and limbic fibers. WM tracks in association fibers are significant related to PM in WD patients. Relative to HC, WD patients showed that the visual association cortex functionally connects to the thalamus and hippocampus, which is associated with global cognitive function in patients with WD. Together, these findings suggested that PM impairment in WD may be modulated by aberrant WM in association fibers, and that GM volume changes in the association cortex has no direct effect on cognitive status, but indirectly affect global cognitive function by its aberrant functional connectivity (FC) in patients with WD. Our findings may provide a new window to further study how WD develops into cognitive impairment, and deepen our understanding of the cognitive status and neuropathology of WD.
Highlights
Wilson’s disease (WD) is an inherited disorder of copper metabolism characterized pathologically by the deposition of copper in many organs, the brain and liver, resulting in numerous clinical symptoms (Bandmann et al, 2015; Czlonkowska et al, 2018)
What are the fundamental brain alternations that lead to cognitive impairment in WD patients? prior studies have reported that WD can cause frontal lobe syndrome, or subcortical dementia, direct evidence of the correlation between brain alternations and neuropsychology is still lacking
We used a multimodal approach to analysis brain structural and functional changes to show that whiter matter (WM) changes in association fibers are associated with prospective memory (PM), and that gray matter (GM) atrophy in the visual association cortex leads to aberrant functional connectivity (FC) that effects global cognitive function in WD
Summary
Wilson’s disease (WD) is an inherited disorder of copper metabolism characterized pathologically by the deposition of copper in many organs, the brain and liver, resulting in numerous clinical symptoms (Bandmann et al, 2015; Czlonkowska et al, 2018). Cognitive impairment is relatively frequent in WD patients, mainly with the frontal lobe syndrome and subcortical dementia (Lang, 1989; Lang et al, 1990). Cognitive impairment greatly affects the quality of life of. PM, which is a memory component most closely related to the planning or goal-making of daily activities, is defined as the future plans or intention of memory (Arnold et al, 2015). Recent studies have reported that PM impairment is associated with gray matter (GM) loss in the basal ganglia (BG) and structural changes in frontal and occipital whiter matter (WM) (Dong et al, 2016, 2019). How structural and functional changes affect PM of WD is still unknown
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