Correlation Between Motor Progression and Structural Connectivity in GBA, LRRK2, and sporadic Parkinson’s Disease (S42.005)

Abstract

<h3>Objective:</h3> To examine longitudinal structural connectivity changes and their correlation to motor symptom progression in people with GBA, LRRK2, or sporadic Parkinson’s disease (PD). <h3>Background:</h3> Monogenetic forms of PD account for 5–10% of PD populations. Compared to LRRK2-related and sporadic PD, GBA-related PD patients have more severe motor symptoms and are at greater risk of developing dementia. We hypothesize differences in motor progression between PD cohorts are associated with changes in structural connectivity. <h3>Design/Methods:</h3> Data were accessed from the Parkinson’s Progressive Markers Initiative (PPMI) project. Subjects were divided into three cohorts: GBA, LRRK2, and sporadic PD (control). Longitudinal connectometry analyses were carried out at baseline, 24 and 48 months, correcting for age, sex, and mean DaTscan striatal binding. We investigated the correlation between white matter tract structural changes, as measured by quantitative anisotropy (QA), and changes in motor symptoms, as measured by Movement Disorders Society-Unified Parkinson’s Rating Scale Part III (MDS-UPDRS III). <h3>Results:</h3> There was a negative correlation between QA of the corpus callosum and corticothalamic tracts and MDS-UPDRS III score in GBA cohorts at 24 (n=11, FDR = 0.0007) and 48 months (n=12, FDR=0.007). The LRRK2 cohorts showed a negative correlation between QA of the corpus callosum, corticospinal, and parietopontine tracts and the MDS-UPDRS III at 48 months only (n=18, FDR=0.025). There were no significant associations in the sporadic cohorts. <h3>Conclusions:</h3> Worsening motor impairment is associated with a decline in structural connectivity in select white matter tracts in GBA-related and LRRK2-related PD, which was not seen in the sporadic PD cohorts. These findings suggest a selective vulnerability of white tracts in monogenic forms of PD. <b>Disclosure:</b> Dr. Yu has nothing to disclose. Miss Wilson has nothing to disclose. An immediate family member of Dr. Rodriguez-Porcel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anmeal. Dr. Rodriguez-Porcel has received publishing royalties from a publication relating to health care. Dr. Cooper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acorda. Dr. Cooper has received research support from NIH. Dr. Cooper has received research support from Ralph H Johnson VA Medical Center.