Cortical connectivity is associated with cognition across time in Parkinson's disease

Cognitive symptoms are common in Parkinson's disease (PD) and have debilitating effects on quality of life and disease trajectory; however, the underlying brain mechanisms remain poorly understood. To address this gap, we investigated the relationship between functional connectivity and cognition at multiple time points using longitudinal functional MRI (fMRI) and cognitive assessments from the Parkinson's Progression Marker Initiative (PPMI). We calculated resting-state functional connectivity across three distinct time points. We analyzed functional connectivity within and between three key cortical brain networks that have been linked with higher-order cognitive function in PD: the frontoparietal network (FPN); the salience network (SAL); and the default mode network (DMN). Global cognitive functioning was assessed with the Montreal Cognitive Assessment (MoCA) at each of the three time points, and this was our primary dependent variable. Linear mixed-effects modeling revealed that decreased FPN-DMN functional connectivity is associated with lower MoCA scores over time. A similar trend was found for SAL-DMN functional connectivity. These relationships were specific to cognition, as there were no significant associations between functional connectivity and motor symptoms, as measured with the Movement Disorders Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III). These findings suggests that cortical connectivity is associated with and may contribute to the progression of cognitive symptoms in PD. Our findings advance knowledge about cognitive changes in PD and emphasize the importance of functional brain network architecture.