Objective: To explore changes in resting-state fMRI (rs-fMRI) functional connectivity networks in PD patients, in areas with prominent dopaminergic and cholinergic innervation.

Background: The pathophysiology of cognitive dysfunction in Parkinson’s disease (PD) implicates major neurotransmitter changes in the dopaminergic and the cholinergic systems.

Method: Data from 88 PD patients without cognitive impairment (mean age 60.02±10.19, disease duration 6.5±7.6 years, MoCA 27.8±1.9) from the Parkinson’s Progression Markers Initiative (PPMI) who performed rs-fMRI were analysed. Patients were stratified according to their performances on Symbol Digit Modalities Test (SDMT) for processing speed (cut-off=34/108) and Benton Judgment of Line Orientation (JLO) for visuospatial skills (cut-off=10/15). Images were preprocessed, and denoised with the CONN toolbox in SPM12, for cholinergic and dopaminergic networks. Seed for the dopaminergic system was the striatum (functionally parcellated into Executive, Motor and Limbic). Seed for the cholinergic system was the Nucleus Basalis of Meynert (NBM). The CIC Atlas was used for target Regions of Interest. Linear regression analysis was performed.

Results: The patients performing above or below SDMT and JLO thresholds did not differ clinically. The PD patients (n=17) who performed below the cut-off for the SDMT, showed decreased dopaminergic and cholinergic connectivity from the Executive Striatum and the NBM to the Left Precentral Gyrus and the Right Inferior Central Gyrus (T=-3.53, P=0.03). Increased cholinergic connectivity from the NBM to the Anterior Insula (T=3.79, P=0.038) and decreased connectivity from the NBM to Postcentral and Middle Temporal Gyrus (T=-3.87, P=0.028) was detected. The patients (n=11) who performed below the cut-off for JLO showed increased dopaminergic connectivity from the Limbic Striatum to the Anterior Cingulate (T=4.36, P=0.002) and cholinergic from the NBM to the pallidum and the posterior Insula (T=3.77, P=0.04). Reduced cholinergic connectivity from the NBM to the Anterior Insula (T=-3.95, P=0.02) was found.

Conclusion: Connectivity changes between subcortical regions critical for dopaminergic and cholinergic networks and various cortical regions mediate the outcome in SDMT and JLO in non-demented PD patients.This abstract was also submitted for presentation at the 2019 EAN conference.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/connectivity-alterations-in-dopaminergic-and-cholinergic-networks-mediate-cognitive-performance-in-patients-with-parkinsons-disease-a-resting-state-fmri-study/