TY - JOUR
T1 - Clinical and dopamine transporter imaging characteristics of leucine rich repeat kinase 2 (LRRK2) and glucosylceramidase beta (GBA) Parkinson's disease participants in the Parkinson's Progression Markers Initiative
T2 - a cross-sectional study
AU - Simuni, Tanya
AU - Brumm, Michael C.
AU - Uribe, Liz
AU - Caspell-Garcia, Chelsea
AU - Coffey, Christopher S.
AU - Siderowf, Andrew
AU - Alcalay, Roy N.
AU - Trojanowski, John Q.
AU - Shaw, Leslie M.
AU - Seibyl, John
AU - Singleton, Andrew
AU - Toga, Arthur W.
AU - Galasko, Doug
AU - Foroud, Tatiana
AU - Nudelman, Kelly
AU - Tosun-Turgut, Duygu
AU - Poston, Kathleen
AU - Weintraub, Daniel
AU - Mollenhauer, Brit
AU - Tanner, Caroline M.
AU - Kieburtz, Karl
AU - Chahine, Lana M.
AU - Reimer, Alyssa
AU - Hutten, Samantha
AU - Bressman, Susan
AU - Marek, Kenneth
AU - Parkinson's Progression Markers Initiative Investigators
AU - Poewe, Werner
AU - Arnedo, Vanessa
AU - Clark, Adrienne
AU - Frasier, Mark
AU - Kopil, Catherine
AU - Chowdhury, Sohini
AU - Sherer, Todd
AU - Daegele, Nichole
AU - Casaceli, Cynthia
AU - Dorsey, Ray
AU - Wilson, Renee
AU - Mahes, Sugi
AU - Salerno, Christina
AU - Crawford, Karen
AU - Casalin, Paola
AU - Malferrari, Giulia
AU - Weisz, Mali Gani
AU - Orr-Urtreger, Avi
AU - Montine, Thomas
AU - Baglieri, Chris
AU - Christini, Amanda
AU - Russell, David
AU - Dahodwala, Nabila
AU - Giladi, Nir
AU - Factor, Stewart
AU - Hogarth, Penelope
AU - Standaert, David
AU - Hauser, Robert
AU - Jankovic, Joseph
AU - Saint-Hilaire, Marie
AU - Richard, Irene
AU - Shprecher, David
AU - Fernandez, Hubert
AU - Brockmann, Katrina
AU - Rosenthal, Liana
AU - Barone, Paolo
AU - Espay, Alberto
AU - Rowe, Dominic
AU - Marder, Karen
AU - Santiago, Anthony
AU - Bressman, Susan
AU - Hu, Shu-Ching
AU - Isaacson, Stuart
AU - Corvol, Jean-Christophe
AU - Ruiz Martinez, Javiar
AU - Tolosa, Eduardo
AU - Tai, Yen
AU - Politis, Marios
AU - Smejdir, Debra
AU - Rees, Linda
AU - Williams, Karen
AU - Kausar, Farah
AU - Williams, Karen
AU - Richardson, Whitney
AU - Willeke, Diana
AU - Peacock, Shawnees
AU - Sommerfeld, Barbara
AU - Freed, Alison
AU - Wakeman, Katrina
AU - Blair, Courtney
AU - Guthrie, Stephanie
AU - Harrell, Leigh
AU - Hunter, Christine
AU - Thomas, Cathi-Ann
AU - James, Raymond
AU - Zimmerman, Grace
AU - Brown, Victoria
AU - Mule, Jennifer
AU - Hilt, Ella
AU - Ribb, Kori
AU - Ainscough, Susan
AU - Wethington, Misty
AU - Ranola, Madelaine
N1 - Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background: There are limited data on the phenotypic and dopamine transporter (DAT) imaging characterization of the Parkinson's disease (PD) patients with leucine rich kinase 2 (LRRK2) and glucosylceramidase beta (GBA) mutations. Objective: The objective of this study was to examine baseline clinical and DAT imaging characteristics in GBA and LRRK2 mutation carriers with early PD compared with sporadic PD. Methods: The Parkinson's Progression Markers Initiative is an ongoing observational longitudinal study that enrolled participants with sporadic PD, LRRK2 and GBA PD carriers from 33 sites worldwide. All participants are assessed annually with a battery of motor and nonmotor scales, 123-I Ioflupane DAT imaging, and biologic variables. Results: We assessed 158 LRRK2 (89% G2019S), 80 GBA (89 %N370S), and 361 sporadic PD participants with the mean (standard deviation) disease duration of 2.9 (1.9), 3.1 (2.0), and 2.6 (0.6) years, respectively. When compared with sporadic PD, the GBA PD patients had no difference in any motor, cognitive, or autonomic features. The LRRK2 PD patients had less motor disability and lower rapid eye movement behavior disorder questionnaire scores, but no meaningful difference in cognitive or autonomic features. Both genetic cohorts had a higher score on the impulse control disorders scale when compared with sporadic PD, but no difference in other psychiatric features. Both genetic PD cohorts had less loss of dopamine transporter on DAT imaging when compared with sporadic PD. Conclusions: We confirm previous reports of milder phenotype associated with LRRK2-PD. A previously reported more aggressive phenotype in GBA-PD is not evident early in the disease in N370s carriers. This observation identifies a window for potential disease-modifying interventions. Longitudinal data will be essential to define the slope of progression for both genetic cohorts. Trial Registration: ClinicalTrials.gov (NCT01141023).
AB - Background: There are limited data on the phenotypic and dopamine transporter (DAT) imaging characterization of the Parkinson's disease (PD) patients with leucine rich kinase 2 (LRRK2) and glucosylceramidase beta (GBA) mutations. Objective: The objective of this study was to examine baseline clinical and DAT imaging characteristics in GBA and LRRK2 mutation carriers with early PD compared with sporadic PD. Methods: The Parkinson's Progression Markers Initiative is an ongoing observational longitudinal study that enrolled participants with sporadic PD, LRRK2 and GBA PD carriers from 33 sites worldwide. All participants are assessed annually with a battery of motor and nonmotor scales, 123-I Ioflupane DAT imaging, and biologic variables. Results: We assessed 158 LRRK2 (89% G2019S), 80 GBA (89 %N370S), and 361 sporadic PD participants with the mean (standard deviation) disease duration of 2.9 (1.9), 3.1 (2.0), and 2.6 (0.6) years, respectively. When compared with sporadic PD, the GBA PD patients had no difference in any motor, cognitive, or autonomic features. The LRRK2 PD patients had less motor disability and lower rapid eye movement behavior disorder questionnaire scores, but no meaningful difference in cognitive or autonomic features. Both genetic cohorts had a higher score on the impulse control disorders scale when compared with sporadic PD, but no difference in other psychiatric features. Both genetic PD cohorts had less loss of dopamine transporter on DAT imaging when compared with sporadic PD. Conclusions: We confirm previous reports of milder phenotype associated with LRRK2-PD. A previously reported more aggressive phenotype in GBA-PD is not evident early in the disease in N370s carriers. This observation identifies a window for potential disease-modifying interventions. Longitudinal data will be essential to define the slope of progression for both genetic cohorts. Trial Registration: ClinicalTrials.gov (NCT01141023).
KW - genetics
KW - Parkinson's disease
UR - https://www.scopus.com/pages/publications/85079588084
U2 - 10.1002/mds.27989
DO - 10.1002/mds.27989
M3 - Article
C2 - 32073681
AN - SCOPUS:85079588084
SN - 0885-3185
VL - 35
SP - 833
EP - 844
JO - Movement Disorders
JF - Movement Disorders
IS - 5
ER -