Steven A Gunzler1, David E Riley2, Shu G Chen3, Curtis M Tatsuoka4, William M Johnson5, John J Mieyal6, Ellen M Walter7, Christina M Whitney8, I Jung Feng9, Harry Owusu-Dapaah10, Shivam O Mittal11, Amy L Wilson-Delfosse12. 1. Parkinson's and Movement Disorders Center, Neurological Institute, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, HAN5040, Cleveland, OH 44106, USA. Electronic address: Steven.Gunzler@UHhospitals.org. 2. InMotion, 4829 Galaxy Parkway, Suite M, Warrensville Heights, OH 44128, USA. 3. Department of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: shu.chen@case.edu. 4. Biostatistics, Neurological Institute, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, HAN5040, Cleveland, OH 44106, USA. Electronic address: curtis.tatsuoka@case.edu. 5. Department of Ophthalmology, Duke University School of Medicine, 2608 Erwin Rd, Durham, NC 27705, USA. Electronic address: will.m.johnson@duke.edu. 6. Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: jjm5@cwru.edu. 7. Parkinson's and Movement Disorders Center, Neurological Institute, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, HAN5040, Cleveland, OH 44106, USA. Electronic address: Ellen.Walter@UHhospitals.org. 8. Parkinson's and Movement Disorders Center, Neurological Institute, University Hospitals Cleveland Medical Center (retired), 11100 Euclid Avenue, HAN5040, Cleveland, OH 44106, USA. 9. Epidemiology & Biostatistics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: ixf34@case.edu. 10. Department of Internal Medicine, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109, USA. Electronic address: howusudapaah@metrohealth.org. 11. Neurology, Columbia Asia Hospitals, Sarjapur Road, Bangalore 560035, India. 12. Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: axw41@case.edu.
Abstract
INTRODUCTION: LRRK2 G2019S mutation carriers with Parkinson's disease (PD) have been generally indistinguishable from those with idiopathic PD, with the exception of variable differences in some motor and non-motor domains, including cognition, gait, and balance. LRRK2 G2019S is amongst the most common genetic etiologies for PD, particularly in Ashkenazi Jewish (AJ) populations. METHODS: This cross-sectional data collection study sought to clarify the phenotype of LRRK2 G2019S mutation carriers with PD. Primary endpoints were the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA). Other motor and non-motor data were also assessed. The Mann-Whitney U Test was utilized to compare LRRK2 G2019S carriers with PD (LRRK2+) with non-carrier PD controls who were matched for age, gender, education, and PD duration. Survival analyses and log rank tests were utilized to compare interval from onset of PD to development of motor and non-motor complications. RESULTS: We screened 251 subjects and 231 completed the study, of whom 9 were LRRK2+, including 7 AJ subjects. 22.73% of AJ subjects with a family history of PD (FH) and 12.96% of AJ subjects without a FH were LRRK2+. There were no significant differences between the 9 LRRK2+ subjects and 19 matched PD controls in MDS-UPDRS, MoCA, or other motor and non-motor endpoints. CONCLUSION: Prevalence of the LRRK2 G2019S mutation in AJ and non-AJ subjects in our study population in Cleveland, Ohio was comparable to other clinical studies. There were no significant motor or non-motor differences between LRRK2+ PD and matched PD controls.
INTRODUCTION:LRRK2 G2019S mutation carriers with Parkinson's disease (PD) have been generally indistinguishable from those with idiopathic PD, with the exception of variable differences in some motor and non-motor domains, including cognition, gait, and balance. LRRK2 G2019S is amongst the most common genetic etiologies for PD, particularly in Ashkenazi Jewish (AJ) populations. METHODS: This cross-sectional data collection study sought to clarify the phenotype of LRRK2 G2019S mutation carriers with PD. Primary endpoints were the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA). Other motor and non-motor data were also assessed. The Mann-Whitney U Test was utilized to compare LRRK2 G2019S carriers with PD (LRRK2+) with non-carrier PD controls who were matched for age, gender, education, and PD duration. Survival analyses and log rank tests were utilized to compare interval from onset of PD to development of motor and non-motor complications. RESULTS: We screened 251 subjects and 231 completed the study, of whom 9 were LRRK2+, including 7 AJ subjects. 22.73% of AJ subjects with a family history of PD (FH) and 12.96% of AJ subjects without a FH were LRRK2+. There were no significant differences between the 9 LRRK2+ subjects and 19 matched PD controls in MDS-UPDRS, MoCA, or other motor and non-motor endpoints. CONCLUSION: Prevalence of the LRRK2 G2019S mutation in AJ and non-AJ subjects in our study population in Cleveland, Ohio was comparable to other clinical studies. There were no significant motor or non-motor differences between LRRK2+ PD and matched PD controls.
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