Abstract
Background: In 2015, the International Parkinson and Movement Disorder Society Task Force recommended research criteria for the estimation of prodromal PD. Objectives: We aimed to evaluate, for the first time, the 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. Methods: Participants were evaluated longitudinally over a period of 5 years (average follow-up: 49.2 ± 12.3 months). Likelihood ratios and probability estimations were calculated based on the International Parkinson and Movement Disorder Society Research Criteria for Prodromal Parkinson's Disease markers and examined for each assessment point. Results: One hundred twenty healthy carriers (49.53 ± 13.4 years; 54% female) and 111 healthy noncarriers (48.43 ± 15.79 years; 49% female) participated in this study. Probability scores were significantly higher in healthy carriers than healthy noncarriers (P < 0.0001). Of the 20 participants (8.6%) who met criteria for probable prodromal PD at baseline, 17 were healthy carriers. 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 nonmotor 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 91.82% (95% confidence interval: 86.69-96.94), sensitivity of 80% (95% confidence interval: 55.21-100), positive predictive value of 47.06% (95% confidence interval: 23.33-70.79), and negative predictive value of 98.06% (95% confidence interval: 95.39-100). 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 future disease modification clinical trials.
Original language | American English |
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Pages (from-to) | 966-973 |
Number of pages | 8 |
Journal | Movement Disorders |
Volume | 33 |
Issue number | 6 |
DOIs | |
State | Published - 1 Jun 2018 |
Keywords
- LRRK2
- MDS prodromal criteria
- Parkinson's disease
- prodromal
All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology