Objective: To prospectively investigate white matter (WM) alterations in non-manifesting carriers (NMCs) of Parkinson’s disease (PD)-related mutations, and its association with likelihood ratio (LR) scores.

Background: Numerous diffusion tensor imaging (DTI) studies demonstrated WM changes in PD patients, as well as in healthy NMCs at risk for PD. However, the relationship between WM damage and LR scores in the prodromal phase remains unclear.

Method: N=58 first-degree relatives of PD patients underwent genetic phenotyping, in addition to MRI scans acquiring DTI datasets, and clinical assessments at baseline and after 2.194±0.4 years. LR scores, fractional anisotropy (FA) and mean diffusivity (MD) indices along major WM pathways were calculated. The association between LR scores and DTI measures was probed using hierarchical regression models adjusting for age and sex.

Results: N= 29 Non-Manifesting Non-Carriers (NMNC) (52.55±10 yrs), N=13 GBA NMC (52.92 ± 9 yrs), and N= 16 LRRK2 NMC (51.37±8.1 yrs) were allocated to three study groups based on genetic phenotyping. Significant between-group differences in FA rate of change were observed in the right inferior frontal occipital fasciculus, right posterior thalamic radiation, and left sagittal striatum (1×3 ANOVA, p<0.05 Bonferroni-corrected). Based on the regression results, LR change was associated with FA levels along the right corticospinal tract, the right hippocampus, and left tapetum at baseline, and the right posterior thalamic radiation, right posterior corona radiate, internal capsule, and fornix measured at follow-up (R2=0.62, p=0.01).

Conclusion: The observed widespread WM alterations might be indicative of ongoing microstructural alterations in the prodromal phase of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-white-matter-microstructural-changes-in-the-prodromal-phase-of-pd-a-2-year-prospective-study/