Early functional network alterations predict motor and cognitive decline in parkinson’s disease

This study aimed to identify potential structural and resting state FC (rs-FC) alterations in de novo PD and examine their possible relationship with motor and cognitive symptoms; and to explore whether early structural and rs-FC alterations were associated with subsequent clinical progression. Seventy-eight de novo PD patients and thirty-one healthy subjects (HS) were enrolled. The severity of motor symptoms was assessed by the MDS-Unified Parkinson’s Disease rating scale and cognitive performance was assessed with the Montreal Cognitive Assessment. Forty out of 78 PD patients underwent a clinical follow-up after a period of 5.29 ± 1.40 years. All participants underwent 3T MRI scanning. Structural MRI analyses included gray matter volume estimation, thalamus, basal ganglia and cerebellar volumetry. Resting-state functional connectivity was assessed using independent component analysis. Compared to HS, de novo PD patients did not show any structural alteration. Conversely, they showed decreased rs-FC in several brain networks, including the default mode network, sensorimotor, cerebellar, medial visual, occipital, orbitofrontal, dorsal attention, executive control, and the left frontoparietal networks. Although baseline functional alterations were not associated with clinical measures at the time of assessment, reduced baseline rs-FC in most resting-state networks was predictive of clinical progression over time. De novo PD patients exhibit widespread rs-FC alterations across multiple brain networks, despite a preserved structural integrity. Early rs-FC alterations in sensorimotor, cerebellar, and cognitive networks were linked to subsequent clinical deterioration. These findings highlight the potential of rs-fMRI as a valuable early imaging correlate for tracking disease progression in PD.