Author Summary Parkinson’s disease (PD) patients with amnestic mild cognitive impairment (e.g., primary processing-speed impairments or primary memory impairments) are at greater risk of developing dementia. Recent evidence suggests that patients with PD and mild cognitive impairment present an altered connectome connectivity. In this work, we further explore the structural connectome of PD patients to provide clues to identify possible sensitive markers of disease progression, and cognitive impairment, in susceptible PD patients. We employed a weighted network framework that yields more stable topological results than the binary network framework and is robust despite graph density differences, hence it does not require thresholding to analyze the connectomes. As Supplementary Information (Colon-Perez et al., 2017), we include databases sharing the results of the network data. Abstract In this study, we investigate the organization of the structural connectome in cognitively well participants with Parkinson’s disease (PD-Well; n = 31) and a subgroup of participants with Parkinson’s disease who have amnestic disturbances (PD-MI; n = 9). We explore correlations between connectome topology and vulnerable cognitive domains in Parkinson’s disease relative to non-Parkinson’s disease peers (control, n = 40). Diffusion-weighted MRI data and deterministic tractography were used to generate connectomes. Connectome topological indices under study included weighted indices of node strength, path length, clustering coefficient, and small-worldness. Relative to controls, node strength was reduced 4.99% for PD-Well ( p = 0.041) and 13.2% for PD-MI ( p = 0.004). We found bilateral differences in the node strength between PD-MI and controls for inferior parietal, caudal middle frontal, posterior cingulate, precentral, and rostral middle frontal. Correlations between connectome and cognitive domains of interest showed that topological indices of global connectivity negatively associated with working memory and displayed more and larger negative correlations with neuropsychological indices of memory in PD-MI than in PD-Well and controls. These findings suggest that indices of network connectivity are reduced in PD-MI relative to PD-Well and control participants.