Basal forebrain (BF) cholinergic projection neurons elaborate a highly extensive input to the cortex. Failure of basal forebrain cholinergic circuits are responsible for the cognitive impairment associated with Wilson’s disease (WD), but whether and how the microstructural changes in fiber projections between the BF and cerebral cortex influence prospective memory (PM) remains poorly understood. We employed diffusion tensor imaging (DTI) data from 21 neurological WD individuals and 26 healthy controls (HC). The experiment reconstructed probabilistic streamline tractography of 18 white matter tracts that correlate with BF cholinergic projections using an Automated fiber quantification (AFQ) toolkit. Tract properties (FA, MD, RD, and AD) were computed for 100 points along each tract for each participant, and their differences between the groups were examined. Subsequently, a Pearson correlation analysis was performed on the patient group to assess the relationship between microstructural alterations and clinical performance. Additional investigations used a tract-based spatial statistics (TBSS) approach to identify regions with altered white matter structure between groups to validate the results of the AFQ study. Compared with HC, the highest non-overlapping DTI-related differences were detected in the anterior thalamic radiation (ATR), corticospinal tract (CST), corpus callosum, association fibers, and limbic system fibers. Additionally, clinical parameters of the patient group were highly correlated with white matter microstructure changes in the cingulum cingulate and inferior longitudinal fasciculus. Our study highlights that the performance of projections between cholinergic input and output areas-the cerebral cortex and BF-may serve as neural biomarkers of PM and prognosis.