Application of the Movement Disorder Society prodromal criteria in healthy G2019S -LRRK2 carriers : Prodromal Criteria Nonmanifesting LRRK2 Carriers

Abstract

<div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d9035491e316">Background</h5> <p id="P1">In 2015 the Movement Disorder Society (MDS) Task Force recommended research criteria for the estimation of prodromal PD. We aimed to evaluate, for the first time, the criteria in first-degree relatives of Ashkenazi Jewish G2019S- <i>LRRK2</i> PD patients, who are considered a population at risk for developing PD, and assess the sensitivity and specificity of the criteria in identifying phenoconverters. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d9035491e324">Methods</h5> <p id="P2">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 Research Criteria for Prodromal Parkinson’s Disease markers and examined for each assessment point. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d9035491e329">Results</h5> <p id="P3">120 healthy carriers (HC) (49.53±13.4 yrs; 54%F) and 111 healthy non-carriers (HNC) (48.43±15.79 yrs; 49%F) participated in this study. Probability scores were significantly higher in HC than HNC (p&lt;0.0001). Of the twenty participants (8.6%) who met criteria for probable prodromal PD at baseline, 17 were HC. Participants who reached the threshold were older (p&lt;0.0001), had higher UPDRS-III (p&lt;0.001), lower cognitive function (p=0.001) and more non-motor symptoms (p&lt;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%CI:86.69–96.94), sensitivity of 80%(95%CI:55.21–100%), PPV of 47.06% (95%CI:23.33–70.79) and NPV of 98.06% (95%CI:95.39–100). All 10 phenoconvertors were G2019S- <i>LRRK2</i> carriers. </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d9035491e337">Conclusions</h5> <p id="P4">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. </p> </div>