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Application of the Movement Disorder Society prodromal criteria in healthy G2019S-LRRK2 carriers.
Mov Disord. 2018 Jul; 33(6):966-973.MD

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. © 2018 International Parkinson and Movement Disorder Society.

Authors+Show Affiliations

Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel. Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel.Departments of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA. Icahn School of Medicine at Mount Sinai, New York, New York, USA.Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel.Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel. Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel.Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel. Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel.Departments of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA.Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.Icahn School of Medicine at Mount Sinai, New York, New York, USA.Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.Genetics Institute, Tel Aviv Medical Center, Tel Aviv, Israel.Genetics Institute, Tel Aviv Medical Center, Tel Aviv, Israel.Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel. Genetics Institute, Tel Aviv Medical Center, Tel Aviv, Israel.Departments of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA. Icahn School of Medicine at Mount Sinai, New York, New York, USA.Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel. Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29603409

Citation

Mirelman, Anat, et al. "Application of the Movement Disorder Society Prodromal Criteria in Healthy G2019S-LRRK2 Carriers." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 33, no. 6, 2018, pp. 966-973.
Mirelman A, Saunders-Pullman R, Alcalay RN, et al. Application of the Movement Disorder Society prodromal criteria in healthy G2019S-LRRK2 carriers. Mov Disord. 2018;33(6):966-973.
Mirelman, A., Saunders-Pullman, R., Alcalay, R. N., Shustak, S., Thaler, A., Gurevich, T., Raymond, D., Mejia-Santana, H., Orbe Reilly, M., Ozelius, L., Clark, L., Gana-Weisz, M., Bar-Shira, A., Orr-Utreger, A., Bressman, S. B., Marder, K., & Giladi, N. (2018). Application of the Movement Disorder Society prodromal criteria in healthy G2019S-LRRK2 carriers. Movement Disorders : Official Journal of the Movement Disorder Society, 33(6), 966-973. https://doi.org/10.1002/mds.27342
Mirelman A, et al. Application of the Movement Disorder Society Prodromal Criteria in Healthy G2019S-LRRK2 Carriers. Mov Disord. 2018;33(6):966-973. PubMed PMID: 29603409.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Application of the Movement Disorder Society prodromal criteria in healthy G2019S-LRRK2 carriers. AU - Mirelman,Anat, AU - Saunders-Pullman,Rachel, AU - Alcalay,Roy N, AU - Shustak,Shiran, AU - Thaler,Avner, AU - Gurevich,Tanya, AU - Raymond,Deborah, AU - Mejia-Santana,Helen, AU - Orbe Reilly,Martha, AU - Ozelius,Laurie, AU - Clark,Lorraine, AU - Gana-Weisz,Mali, AU - Bar-Shira,Anat, AU - Orr-Utreger,Avi, AU - Bressman,Susan B, AU - Marder,Karen, AU - Giladi,Nir, AU - ,, Y1 - 2018/03/30/ PY - 2017/10/05/received PY - 2018/01/10/revised PY - 2018/01/17/accepted PY - 2018/4/1/pubmed PY - 2019/9/4/medline PY - 2018/4/1/entrez KW - LRRK2 KW - MDS prodromal criteria KW - Parkinson's disease KW - prodromal SP - 966 EP - 973 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov. Disord. VL - 33 IS - 6 N2 - 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. © 2018 International Parkinson and Movement Disorder Society. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/29603409/Application_of_the_Movement_Disorder_Society_prodromal_criteria_in_healthy_G2019S_LRRK2_carriers_ L2 - https://doi.org/10.1002/mds.27342 DB - PRIME DP - Unbound Medicine ER -