Objective: We aimed to investigate the dynamics of inter-network connectivity among non-manifesting GBA and LRRK2 mutation carriers.

Background: The prodromal phase of Parkinson’s disease (PD) is characterized by sustained motor and cognitive functioning despite the ongoing sub-clinical neurodegeneration processes. Non‐manifesting carriers of mutations in the LRRK2 and GBA genes represent an “at risk” cohort for future development of PD.

Method: Seventy-five (39 females; mean age ± SD= 52.38 ±9.27) participants underwent 3T MRI scans acquiring 3D T1-weighted and resting-state fMRI (rs-fMRI) datasets. All participants underwent genetic testing and a comprehensive motor, cognitive, and affective assessments. Region of interest (ROI)-to-ROI connectivity using CONN toolbox was carried out to explore inter-network connectivity dynamics among the brains’ major functional networks including; the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN), salience, and cerebellar networks.

Results: Thirty-two non-manifesting non-carriers (NMNC) (53.28±10.7), 19 GBA non-manifesting carriers (NMC) (52.73±8.9), and 24 LRRK2 NMC (50.82±7.4) were included in this study. No significant differences in age (1×3 ANOVA; p > 0.05), and gender (chi-square test; p > 0.05) were detected between the study groups. Additionally, the three groups didn’t differ significantly in motor performance, and MoCA test scores (1×3 ANOVA; p > 0.05). Functionally, comparable inter-network connectivity patterns were observed between LRRK2-NMC carriers and NMNC. However, GBA-NMC demonstrated connectivity reduction within-and – between task positive networks, as well as an increase of inter-network connections between task-positive and task-negative networks (i.e DMN and salience) (p < 0.05; FDR-corrected).

Conclusion: GBA-NMC demonstrated different inter-network connectivity patterns among task positive and task negative networks compared with NMNC and LRRK2-NMC, behavioral correlations are warranted to better understand the significance of these findings.

References: GBA-NMC demonstrated different inter-network connectivity patterns among task positive and task negative networks compared with NMNC and LRRK2-NMC, behavioral correlations are warranted to better understand the significance of these findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/inter-network-connectivity-dynamics-underlie-compensatory-mechanisms-in-prodromal-parkinsons-disease/