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Degeneration of Corticostriatal Fibers in Parkinson's Disease and their Differential Relations to Cognitive and Motor Deficits

Zhang, Y; Wu, K; Buckley, S; Mendick, S; Seibyl, J; Foster, E; Coffey, C; Marek, K; Schuff; N; The Parkinson\'s Progression Markers Initiative
 
2014-06-09
MDS: Stockholm, Sweden
Download Presentation: 2014MDS poster262 yz.pdf
 
Abstract:
Objective: The study aimed to: 1) reliably identify corticostriatal fibers that are associated with cognitive and motor functions using diffusion tensor imaging (DTI) data from the Parkinson's Progression Marker Initiative (PPMI), 2) determine differences in fiber integrity between patients with Parkinson's Disease (PD) and healthy controls, and 3) assess fiber degeneration in relation to the degree of cognitive and motor deficits in PD.

Background: Functional MRI and DTI studies have suggested alterations of corticostriatal connections in PD, in addition to nigrostriatal fiber connections, as we have shown recently. The integrity of these connections could provide markers for tracking cognitive and motor deficits in PD differentially.

Methods: DTI data from 46 de-novo and drug naïve PD patients and 25 healthy subjects participating in the PPMI were selected in the order of scans and analyzed. Cognitive performance of memory, executive and attention was scored using MDS assessments and standardized for each domain. Motor performance was measured using total MDS-UPDRS-III. All patients had DTI scans using 3 Tesla MRI. Fiber tracking was performed using TrackVis. Integrity was measured using the mean fractional anisotropy (FA) along each fiber. Side of symptom onset was used to define the most and least affected hemisphere. For controls and patients with symmetrical onset, DTI data of left/right brain hemisphere were averaged. FA associations with motor scores were covariate for the degree of cognitive deficits and vice versus.

Results: Three types of fibers were traced: (1) executive loop, connecting dorsolateral prefrontal cortex (DLPFC) with the anterior putamen; (2) motor loop, connecting supplementary motor area (SMA) with the posterior putamen; and (3) dopaminergic fibers, connecting substantia nigra (SN) to pallidum and inferior putamen (Put/Gp). Compared to controls, PD patients had bilaterally reduced FA of dopaminergic fibers, whereas FA of the other fibers was normal. In PD, reduced FA of dopaminergic fibers was significantly correlated with increased motor deficits at the most affect side. In addition, reduced FA of the executive loop was correlated with the degree of executive deficits at the most affected side, regardless of the degree of motor impairment.

Conclusions: The findings suggest that degradation of specific corticostriatal fibers potentially provide a marker of clinically relevant cognitive and motor impairments in early PD.