Application of the Movement Disorder Society Prodromal Criteria in Healthy G2019S-LRRK2 Carriers (S3.002)

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. The utility of the criteria in a risk cohort of healthy carriers of the G2019S-LRRK2 mutation has never been examined. Design/Methods: Participants were evaluated longitudinally over a period of 5 years (average follow-up 49.2±12.3 months). 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 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 modifying clinical trials. Study Supported by: Michael J Fox Foundation for Parkinson’s Research Disclosure: Dr. Mirelman has nothing to disclose. Dr Saunders-Pullman has nothing to disclose. Dr. Alcalay has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Denali, Prophase, Genzyme Sanofi. Dr. Shustak has nothing to disclose. Dr. Thaler has nothing to disclose. Dr. Raymond has nothing to disclose. Dr. Mejia Santana has nothing to disclose. Dr. Orbe-Reilly has nothing to disclose. Dr. Ozelius has nothing to disclose. Dr. Clark has nothing to disclose. Dr. Gana-Weiss has nothing to disclose. Dr. Bar-Shira has nothing to disclose. Dr. Orr-Urtreger has nothing to disclose. Dr. Bressman has nothing to disclose. Dr. Marder has nothing to disclose. Dr. Giladi has nothing to disclose.