Structural network topology correlates with cognitive impairment in Parkinson’s disease

Abstract

In patients with Parkinson's disease (PD), cognitive impairment is common and substantially exacerbates disease severity. The objective of this study is to investigate whether cognitive decline affects disease severity and whether structural network disruption contributes to cognitive impairment in PD patients. PD patients (n = 146) receiving structural and functional magnetic resonance imaging from Parkinson's Progression Markers Initiative (PPMI) database were included. Based on the scores of Symbol Digit Modalities Test (SDMT), patients were classified into lower quartile group (SDMT score rank: 0%~25%), interquartile group (SDMT score rank: 26%~75%), and upper quartile group (SDMT score rank: 76%~100%) according to their SDMT score quartiles to assess how cognitive function shapes disease manifestations and brain network topology. Patients in the lower quartile group exhibited more severe motor symptoms, non-motor symptoms, and striatal dopamine depletion compared to interquartile group and upper quartile group. In addition, they also showed impaired structural network topology both at global and local levels compared to interquartile group and upper quartile group. Furthermore, different nodal network metrics in structural network contributed to cognitive and motor impairment of PD patients. Taken together, PD patients with worse cognitive function exhibited more severe motor and non-motor symptoms and aberrant structural network metrics were associated with both cognitive and motor decline of PD patients.

Structural network topology mediated cognitive impairment in Parkinson’s disease

“…These findings suggested that structural network impairments contributed to depression in PD patients. In current study, we revealed BC of right middle temporal gyrus in structural network was higher in CI+ patients than CI-patients, which was consistent with our recent study showing PD patients with lower SDMT scores exhibited greater BC of right middle temporal gyrus than PD patients with higher SDMT scores [49]. Here, we demonstrated that BC of right middle temporal gyrus mediated the effects of depressive symptoms on MoCA scores and CI of PD patients, suggesting higher BC of right middle temporal gyrus in PD was causally correlated with PD-related CI.…”

“…In addition, we also revealed age-dependent increase in BC of right middle temporal gyrus was causally associated with CI in PD. In agreement with these results, recently, we also revealed DC of right superior occipital gyrus and BC of right middle temporal gyrus mediated the negative association between age and cognitive function of PD patients [49]. To summarize, our findings suggested that local topological metrics were associated with age-dependent cognitive decline in PD patients.…”

“…Here, we demonstrated that BC of right middle temporal gyrus mediated the effects of depressive symptoms on MoCA scores and CI of PD patients, suggesting higher BC of right middle temporal gyrus in PD was causally correlated with PD-related CI. Importantly, the significant association between BC of right middle temporal gyrus and cognitive function of PD patients has been confirmed in our recent study [49]. Taken together, our findings suggested that depression contributed to CI in PD via the regulation of local topological metrics in right middle temporal gyrus.…”

“…Therefore, a major contributor of our study to the filed was that we provided network-level explanations to the associations between age, EDS, depression and cognitive decline in PD patients. Importantly, we identified some key nodes, such as right middle temporal gyrus and right superior occipital gyrus, were network mediators of cognitive decline in PD patients, which have been confirmed in a recent study [49].…”

“…Consistently, most of these nodal metrics also exhibited cognitive level-dependent changes in PD patients [49]. Therefore, PD patients with CI displayed consistently specific patterns of structural network topology compared to PD patients without CI.…”