Tanya Simuni1, Michael C Brumm2, Liz Uribe2, Chelsea Caspell-Garcia2, Christopher S Coffey2, Andrew Siderowf3, Roy N Alcalay4, John Q Trojanowski5, Leslie M Shaw5, John Seibyl6, Andrew Singleton7, Arthur W Toga8, Doug Galasko9, Tatiana Foroud10, Kelly Nudelman10, Duygu Tosun-Turgut11, Kathleen Poston12, Daniel Weintraub13, Brit Mollenhauer14, Caroline M Tanner11, Karl Kieburtz15, Lana M Chahine16, Alyssa Reimer17, Samantha Hutten17, Susan Bressman18, Kenneth Marek6. 1. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2. Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA. 3. Departments of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 4. Department of Neurology, The Taub Institite for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA. 5. Departments of Pathology and Laboratory Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 6. Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. 7. Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, Maryland, USA. 8. Laboratory of Neuroimaging (LONI), University of Southern California, Los Angeles, California, USA. 9. Department of Neurology, University of California, San Diego, California, USA. 10. Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA. 11. Department of Neurology, University of California San Francisco, San Francisco, California, USA. 12. Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA. 13. Departments of Psychiatry and Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 14. Department of Neurology, University Medical Center Goettingen, Goettingen, Germany and Paracelsus-Elena-Klinik, Kassel, Germany. 15. Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA. 16. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 17. The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA. 18. Icahn School of Medicine, Mount Sinai, New York, New York, USA.
Abstract
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).
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).
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Authors: Eileen E Moran; Susan B Bressman; Roberto A Ortega; Deborah Raymond; William C Nichols; Christina A Palmese; Sonya Elango; Matthew Swan; Vicki Shanker; Imali Perera; Cuiling Wang; Molly E Zimmerman; Rachel Saunders-Pullman Journal: Front Neurol Date: 2021-02-26 Impact factor: 4.003
Authors: Myung Jun Lee; Kyoungjune Pak; Han-Kyeol Kim; Kelly N Nudelman; Jong Hun Kim; Yun Hak Kim; Junho Kang; Min Seok Baek; Chul Hyoung Lyoo Journal: NPJ Parkinsons Dis Date: 2021-11-26
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