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: A Cross-Sectional Study

Tanya Simuni; Michael C Brumm; Liz Uribe; Chelsea Caspell-Garcia; Christopher S Coffey; Andrew Siderowf; Roy N Alcalay; John Q Trojanowski; Leslie M Shaw; John Seibyl; Andrew Singleton; Arthur W Toga; Doug Galasko; Tatiana Foroud; Kelly Nudelman; Duygu Tosun-Turgut; Kathleen Poston; Daniel Weintraub; Brit Mollenhauer; Caroline M Tanner; Karl Kieburtz; Lana M Chahine; Alyssa Reimer; Samantha Hutten; Susan Bressman; Kenneth Marek; Parkinson's Progression Markers Initiative Investigators

doi:10.1002/mds.27989

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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: A Cross-Sectional Study

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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: A Cross-Sectional Study

Tanya Simuni, Michael C Brumm, Liz Uribe, Chelsea Caspell-Garcia, Christopher S Coffey, Andrew Siderowf, Roy N Alcalay, John Q Trojanowski, Leslie M Shaw, John Seibyl, …

Movement disorders, Vol.35(5), pp.833-844

05/2020

DOI: 10.1002/mds.27989

PMCID: PMC7231646

PMID: 32073681

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Abstract

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. 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. 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. 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. 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. ClinicalTrials.gov (NCT01141023). © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Cross-Sectional Studies

Disabled Persons

Dopamine Plasma Membrane Transport Proteins - genetics

Glucosylceramidase - genetics

Humans

Leucine

Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics

Longitudinal Studies

Motor Disorders

Mutation - genetics

Parkinson Disease - diagnostic imaging

Parkinson Disease - genetics

Details

Title: Subtitle: 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: A Cross-Sectional Study
Creators: Tanya Simuni - Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
Michael C Brumm - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA
Liz Uribe - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA
Chelsea Caspell-Garcia - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA
Christopher S Coffey - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA
Andrew Siderowf - Departments of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Roy N Alcalay - Department of Neurology, The Taub Institite for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
John Q Trojanowski - Departments of Pathology and Laboratory Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Leslie M Shaw - Departments of Pathology and Laboratory Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
John Seibyl - Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA
Andrew Singleton - Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, Maryland, USA
Arthur W Toga - Laboratory of Neuroimaging (LONI), University of Southern California, Los Angeles, California, USA
Doug Galasko - Department of Neurology, University of California, San Diego, California, USA
Tatiana Foroud - Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA
Kelly Nudelman - Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA
Duygu Tosun-Turgut - Department of Neurology, University of California San Francisco, San Francisco, California, USA
Kathleen Poston - Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA
Daniel Weintraub - Departments of Psychiatry and Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Brit Mollenhauer - Department of Neurology, University Medical Center Goettingen, Goettingen, Germany and Paracelsus-Elena-Klinik, Kassel, Germany
Caroline M Tanner - Department of Neurology, University of California San Francisco, San Francisco, California, USA
Karl Kieburtz - Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
Lana M Chahine - Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Alyssa Reimer - The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA
Samantha Hutten - The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA
Susan Bressman - Icahn School of Medicine, Mount Sinai, New York, New York, USA
Kenneth Marek - Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA
Parkinson's Progression Markers Initiative Investigators
Resource Type: Journal article
Publication Details: Movement disorders, Vol.35(5), pp.833-844
DOI: 10.1002/mds.27989
PMID: 32073681
PMCID: PMC7231646
NLM abbreviation: Mov Disord
ISSN: 0885-3185
eISSN: 1531-8257
Grant note: U19 AG062418 / NIA NIH HHS
Language: English
Date published: 05/2020
Academic Unit: Biostatistics
Record Identifier: 9984214716702771

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