Objective: To examine change in clinical characteristics in LRRK2 G2019S carriers with Parkinson’s disease (PD) and without PD (non-manifest carriers) enrolled in Virtual Assessment of LRRK2 carriers to Optimize Parkinson’s disease research (VALOR-PD) over two years.

Background: The LRRK2 G2019S variant is a common genetic cause of PD and exhibits incomplete penetrance. Long-term, longitudinal studies are needed to identify the earliest signs of LRRK2 PD and understand the transition to PD.

Method: In this 36-month remote study, LRRK2 G2019S carriers with and without investigator-determined PD complete annual on-line assessments and video-based visits. Participants complete assessments of motor and non-motor symptoms (Epworth Sleepiness Scale, Beck Depression Inventory-II, Parkinson Anxiety Scale, Scales for Outcomes in Parkinson’s disease-Autonomic Dysfunction (SCOPA-AUT), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts Ib and II). Participants undergo a modified motor examination (MDS-UPDRS Part III) and non-motor assessment (MDS-UPDRS Part 1a) with an investigator and cognitive assessment (Montreal Cognitive Assessment) with a study coordinator. Mean (standard deviation) or n (%) are reported for each assessment at each time point over two years. Generalized estimating equations model the change from baseline to follow-up or the binary response at follow-up while adjusting for the baseline value. Multiple testing is accounted for by applying Bonferroni correction.

Results: At baseline, 66 LRRK2 carriers with PD were mean (SD) age 67.7 (8.7) (96% white, 50% female, 80% Ashkenazi Jewish) and 211 without PD were age 53.3 (15.0) (95% white, 59% female, 73% Ashkenazi Jewish). At year one, 65 (98%) with PD and 199 (94%) without PD completed assessments. At year two, 56 (85%) with PD and 192 (91%) without PD completed assessments. LRRK2 carriers with PD scored worse than non-manifest carriers on several clinical assessments at every time point. With the exception of the SCOPA-AUT (p=0.004), there were no significant between group differences in rates of longitudinal change over two years (Table 1).

Conclusion: Over two years, longitudinal change in most clinical assessment scores did not differ between groups. Longer follow up and more sensitive measures of disease progression are needed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-change-in-clinical-characteristics-of-lrrk2-carriers-in-a-remote-cohort/