Session Information
Date: Monday, October 8, 2018
Session Title: Parkinson's Disease: Genetics
Session Time: 1:15pm-2:45pm
Location: Hall 3FG
Objective: To evaluate the MDS prodromal criteria in first-degree relatives of Ashkenazi Jewish G2019S-LRRK2 PD patients, who are considered a population at risk for developing PD, and assess the sensitivity and specificity of the criteria in identifying phenoconverters.
Background: The pathological changes of Parkinson’s disease (PD) can start decades before the appearance of cardinal motor symptoms. Detecting patients at the premotor stage will be crucial for future clinical trials aiming at modifying progression at the earliest stages of the disease. In 2015 the Movement Disorder Society (MDS) Task Force recommended research criteria for the estimation of prodromal PD.
Methods: Participants were evaluated longitudinally over a period of 5 years (average follow-up 49.2±12.3months). Likelihood ratios (LR) and probability estimations were calculated based on the MDS criteria markers and examined for each assessment point.
Results: 120 healthy carriers (HC) (49.53±13.36yrs; 50%F) and 111 healthy non-carriers (HNC) (48.43±15.79yrs; 48%F) participated in this study. Probability scores without genetic status were already significantly higher in HC than HNC (p=0.038). Twenty participants (8.6%) met criteria for probable prodromal PD at baseline, 17 were HC. Participants who reached the threshold were older (p<0.0001), had higher UPDRS-III (p<0.001), lower cognitive function (p=0.001) and more non-motor symptoms (p<0.0001), compared to those who did not. Ten participants were diagnosed with incident-PD within 5 years from baseline resulting in a specificity of 93.85%(95%CI:90.83-96.86), sensitivity of 80%(95%CI:55.21-100%), PPV of 34.78% (95%CI:15.31- 54.24) and NPV of 99.13% (95%CI:97.94-100). All 10 phenoconvertors were G2019S-LRRK2 carriers.
Conclusions: The results showed the utility of using the criteria and high sensitivity and specificity in identifying prodromal PD in this high risk unique cohort. These results may be valuable for disease prevention and future disease modification clinical trials.
To cite this abstract in AMA style:
A. Mirelman, R. Saunders-Pullman, R. Alcalay, S. Shustak, A. Thaler, B. Cohen, A. Hillel, T. Gurevich, D. Raymond, H. Mejia-Santana, L. Ozelius, L. Clark, M. Gana-Weisz, A. Bar-Shira, A. Orr-Urtreger, S. Bressman, K. Marder, N. Giladi. Application of the Movement Disorder Society Prodromal Criteria in healthy G2019S-LRRK2 carriers [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/application-of-the-movement-disorder-society-prodromal-criteria-in-healthy-g2019s-lrrk2-carriers/. Accessed May 21, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/application-of-the-movement-disorder-society-prodromal-criteria-in-healthy-g2019s-lrrk2-carriers/