This study is designed to investigate the brain function changed regions in elderly patients with knee osteoarthritis (KOA) and to explore the relationship between neuropsychological tests and resting-state functional magnetic resonance imaging (rs-fMRI) network to clarify the possible mechanism underlying cognitive changes in KOA patients.Fifty-two patients aged ≥ 65 with KOA and twenty-two healthy-matched controls were recruited in this study. All participants were given rs-fMRI check. We used graph theory analysis to characterize functional connectivity (FC) and topological organization of the brain structural network. The relationship between FC values, topological properties, and the neuropsychological test scores was analyzed.Compared with the controls, fourteen edges with lower functional connectivity were noted in the KOA group. Local efficiency and small-worldness of KOA patients decreased compared to the healthy controls. No significant alterations of nodal topological properties were found between the two groups. There was a significant positive correlation between the AVLT-H (L) and the internetwork of default mode network (DMN) (left/right orbitofrontal Superior cortex) and limbic/cortical areas (left/right caudate, right amygdala). AVLT-H(L) was positively correlated with small-worldness and local efficiency.The results indicated that for elderly KOA patients with declined cognition, topological properties, FC between DMN and subcortical limbic network related regions are significantly decreased compared to healthy controls. These alterations demonstrated a significant correlation with the neuropsychological test scores.Copyright © 2022 Lin, Lan, Wu, Cao, Li, Qi, Liu, Yang, Lu and Wang.