Objective: To compare baseline clinical and imaging characteristics of the GBA and LRRK2 PD manifest cohorts to PD sporadic (sPD) cohort.

Background: The phenotype and natural history of LRRK2 and GBA Parkinson disease (PD) have not been fully established.

Method: We analyzed data from the Parkinson’s Progression Markers Initiative (PPMI). Analysis was adjusted for gender and disease duration.

Results: At the time of data download (11.5.2018), the study enrolled 155 LRRK2 (88.4% G2019S) and 82 GBA (88 %N370S) PD via study sites and worldwide recruitment initiatives compared to 366 sporadic PD (sPD) participants. The median PD duration in GBA and LRRK2 cohorts at recruitment was 38.7 (0.3-110) and 31.5 (1-104) months respectively. Comparison was made to sPD cohort at 2 year study visit, median disease duration 31.4(6.9). The average age of the LRRK2/GBA/sPD cohorts was 64 (9.2)/63 (9.7)/64(9.7) years (p>0.5), 55/46/34 % females respectively. Compared to sPD, LRRK2 had significantly lower scores on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, less tremor dominant (TD) subjects, better smell test (UPSIT), lower RBD, higher anxiety (STAI trait) scores while GBAs had no difference on MDS-UPDRS Part I-III but higher Part IV scores, less TD subjects, lower UPSIT and higher proportion of anosmics, no difference in RBD or sleepiness (ESS) scores. There was no difference in Montreal Cognitive Assessment (MoCA), depression scores and dopaminergic drugs utilization (LEDD) between the groups. There was no difference in cognitive or psychiatric features between GBA and LRRK2 cohorts.  Both genetic cohorts had higher (better) DAT striatal binding compared to sPD. At the time of the analysis only a subset of genetic cohort had results of spinal fluid biologics analysis and there was a trend for lower A-beta in GBA cohort.

Conclusion: As previously reported, GBA and LRRK2 PD cohorts have distinct clinical features though the difference is subtle and does not involve cognitive domain. These observations create a window of opportunity for early targeted disease modifying interventions. Higher DAT striatal binding in LRRK2 and GBA cohorts might reflect compensatory mechanisms unique to genetic cohorts. Longitudinal data will be essential to establish trajectory of progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-imaging-characteristics-of-manifest-lrrk2-and-gba-carriers-the-ppmi-cohort/