Category: Parkinson's Disease: Neuroimaging
Objective: We aimed to study the association between presynaptic striatal dopamine uptake and functional connectivity (FC) patterns among healthy first-degree relatives of PD patients with mutations in LRRK2 and GBA.
Background: Non-manifesting carriers (NMC) of Parkinson’s disease (PD)-related mutations such as LRRK2 and GBA are at an increased risk for developing PD. Dopamine transporter spectral positron emission computed tomography (DaT-SPECT) is widely used for capturing functional nigro-striatal dopaminergic activity. However, it does not reflect other ongoing neuronal processes; especially in the prodromal stages of the disease. Resting-state fMRI (rs-fMRI) has been proposed as a mode for assessing reactive compensatory processes associated with PD, but its relation to dopaminergic deficiency remains unclear.
Method: 85 healthy first-degree subjects were enrolled and genotyped. All participants underwent DaT-SPECT and rs-fMRI scans, as well as a comprehensive clinical assessment battery. Between-group differences in FC within striatal regions were investigated and compared with striatal binding ratios (SBR).
Results: N=26 GBA, N= 25 LRRK2 NMC, and N=34 age-matched NM-NC were included in each study group based on genetic phenotypic results. While genetically-defined groups were similar across clinical measures, LRRK2-NMC demonstrated lower SBR in the right putamen compared with NM-NC, and higher right putamen FC compared to GBA-NMC. In this group, higher striatal FC was associated with increased risk for PD.
Conclusion: The observed differential SBR and FC patterns among LRRK2-NMC and GBA-NMC indicates that DaT-SPECT and FC assessment offers a sensitive prediction of the likelihood risk for PD in the pre-clinical stages of the disease.
To cite this abstract in AMA style:
A. Droby, M. Artzi, H. Lerman, RM. Hutchison, D. Ben Bashat, N. Omer, T. Gurevich, A. Orr-Urtreger, B. Cohen, J. Cedarbaum, E. Even Sapir, N. Giladi, A. Mirelman, A. Thaler. Aberrant dopamine transporter and functional connectivity patterns in LRRK2 and GBA non-manifesting carriers [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/aberrant-dopamine-transporter-and-functional-connectivity-patterns-in-lrrk2-and-gba-non-manifesting-carriers/. Accessed September 7, 2024.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/aberrant-dopamine-transporter-and-functional-connectivity-patterns-in-lrrk2-and-gba-non-manifesting-carriers/