Session Information
Date: Tuesday, September 24, 2019
Session Title: Parkinsonisms and Parkinson-Plus
Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: To examine baseline clinical and dopamine transporter (DAT) imaging characteristics in a cohort of non-manifest carriers (NMC) of GBA and LRRK2 compared to healthy controls (HC) in the PPMI cohort.
Background: LRRK2 and GBA mutations are most common types of monogenic causes of Parkinson disease (PD). The clinical and biomarker characteristics of non-manifesting mutation carriers have not been fully described.
Method: Parkinson’s Progression Markers Initiative (PPMI) is a longitudinal ongoing controlled study of at baseline de novo PD participants, HC and carriers of PD relevant genetic mutations. All participants are assessed annually with comprehensive motor and non-motor scales, DAT imaging and biologic variables.
Results: The study enrolled 194 LRRK2 (91% G2019S) and 132 GBA (96 %N370S) NMCs via study sites and worldwide recruitment initiatives. NMCs were average age was 61.9 (7.1) years, 60% female, and 87% had first-degree PD relative. 25% of LRRK2 and 9% of GBA NMCs had abnormal DAT scan (defined as <80% of age expected lowest putamen SBR). Compared to HC, both LRRK2 and GBA NMCs had significantly higher scores on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total, Part I, II, III, and lower Montreal Cognitive Assessment (MoCA), scores that were independent of DAT results. There was no difference in daytime sleepiness and REM behavior disorder scores. Hyposmia was significantly more common and predicted DAT scan deficit only in LRRK2. NMCs without DAT deficit showed increase in DAT striatal binding compared to HC.
Conclusion: Our data demonstrate evidence of subtle PD motor and non-motor signs in NMCs that can precede DAT abnormalities with some differences between LRRK2 and GBA NMCs. Increase in DAT striatal binding in some NMCs might reflect compensatory mechanisms early in the prodromal phase. Longitudinal data will be essential to confirm our data, and establish risk factors and trajectory for development of motor parkinsonism.
To cite this abstract in AMA style:
A. Siderowf, T. Simuni, L. Uribe, C. Caspell-Garcia, H. Cho, C. Coffey, T. Foroud, B. Mollehauer, C. Tanner, K. Kieburtz, L. Chahine, D. Weintraub, K. Marek. Clinical and imaging characteristics of non-manifest LRRK2 and GBA carriers: The PPMI cohort [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/clinical-and-imaging-characteristics-of-non-manifest-lrrk2-and-gba-carriers-the-ppmi-cohort/. Accessed June 15, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-imaging-characteristics-of-non-manifest-lrrk2-and-gba-carriers-the-ppmi-cohort/