Objective: To evaluate new cases of prodromal PD and concern for parkinsonism in a cohort of LRRK2 G2019S carriers.

Background: LRRK2 G2019S is a common cause of genetic PD that exhibits reduced penetrance. A better understanding of the transition from non-manifest to prodromal to manifest disease is needed. The Movement Disorder Society (MDS) prodromal PD criteria may be one strategy for identifying those at greatest risk of developing PD.

Method: Among LRRK2 G2019S carriers ≥ 50 years of age without PD enrolled in a prospective, longitudinal, remote study, we used the MDS prodromal PD criteria to calculate an overall likelihood ratio at each annual visit. Those with a likelihood ratio that exceeded the age-based minimum likelihood ratio necessary to meet the recommend 80% threshold were classified as prodromal PD.  During video-based visits, movement disorder experts blinded to self-reported PD status conducted a modified MDS – Unified Parkinson Disease Rating Scale (UPDRS) motor examination and identified cases of concern for parkinsonism.

Results: At baseline, 8% (10/127) of non-manifest participants ≥ 50 years of age met criteria for prodromal PD and 9% (20/217) of all non-manifest participants demonstrated parkinsonism.  At year one, 9% (11/126) met criteria for prodromal PD and 7% (14/204) demonstrated parkinsonism.  As of March 2022, at year two, 7% (7/94) met criteria for prodromal PD and 11% (15/136) demonstrated parkinsonism. One participant had prodromal PD and 3 had a concern for parkinsonism at baseline, year one, and year two consistently. Between baseline and year one, 7 new cases of parkinsonism and 3 new cases of prodromal PD were identified, with 2 participants meeting both criteria. Between year one and year two, 4 new cases of parkinsonism and 3 new cases of prodromal PD have been identified to date, with 2 participants meeting both criteria. Table 1 summarizes the change in motor, mood, and symptom scores for these 13 emergent cases. Of participants with prodromal PD and/or concern for parkinsonism there have been no new cases of self-reported PD.
[Table 1]
[Table 2]

Conclusion: While there have been a similar number of cases of parkinsonism and/or prodromal PD from year to year, designations have been unstable. Moreover, 13 new cases were identified over a short period of follow-up. The instability in designation may reflect limitations of the remote motor examination or fluctuations of symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/newly-identified-cases-of-parkinsonism-and-prodromal-pd-in-a-remote-lrrk2-g2019s-cohort/