Structural network topology mediated cognitive impairment in Parkinson's disease

Cognitive impairment (CI) is one of the most prominent non-motor symptoms in Parkinson's disease (PD). How brain network abnormalities contribute to CI in PD patients remain largely unclear. The goal of this study is to explore whether aberrations of brain network topology were causally associated with cognitive decline in PD patients. PD patients receiving magnetic resonance imaging from Parkinson's Progression Markers Initiative (PPMI) database were specifically selected. According to the scores of Montreal Cognitive Assessment (MoCA), PD patients were classified into CI+ group (MoCA score ≤ 25) and CI- group (MoCA score > 25) to investigate whether clinical features and brain networks were significantly different between two groups. Mediation analysis was utilized to evaluate whether brain network alterations contributed to CI in PD patients. We revealed CI + group exhibited more severe non-motor symptoms compared to CI- group. In addition, age, excessive daytime sleepiness, and depressive symptoms were found to be significantly associated with CI of PD patients. Moreover, CI+ group exhibited statistically different local topological properties in structural network compared to CI- group. Furthermore, differential local topological metrics in structural network meditated the effects of age, excessive daytime sleepiness, and depression on cognitive decline of PD patients. Taken together, out study suggested that PD patients with CI exhibited notable disturbances of structural network topology, which mediated negative associations between of age, excessive daytime sleepiness, depression and cognitive decline of PD patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by grants from National Natural Science Foundation of China (Grant No. 81873778, 82071415) and National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (Grant No. NRCTM(SH)-2021-03). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The PPMI study was approved by the Ethics Committee of all participating sites and all participants signed informed consent prior to participation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All the raw data used in the preparation of this Article were downloaded from PPMI database (www.ppmi-info.org/data).All data produced in the present study are available upon reasonable request to the authors.