دانلود رایگان مقاله انگلیسی ویژگی های حرکتی و غیر حرکتی بیماری پارکینسون در حامل های LRRK2 G2019S - الزویر 2018

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 among 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.

Discussion

 There is a heterogeneity of PD clinical subtypes as well as a variety of genes that have been implicated in PD. In order to better predict future PD symptomatology as well as to tailor treatment to a particular genotype, the phenotypes of genetic PD must be better defined. This cross-sectional data collection study demonstrated no significant differences in motor and nonmotor phenotype between LRRK2+ subjects and matched controls in our study population. The prevalence of LRRK2 G2019S carrier status was 12.96% and 1.13% amongst AJ and non-AJ subjects respectively, with a prevalence of 22.73% amongst AJ subjects with a FH of PD, in this study population in Cleveland, Ohio. This represents a similar prevalence in our AJ population compared to other series of AJ subjects with PD.[2, 3] This report, to our knowledge, is the first description of the prevalence of LRRK2 carrier status amongst AJ and non-AJ subjects at a mid-western medical center in the United States. Motor and non-motor characteristics of PD, such as gait and cognition, can be influenced by age and duration of disease. Additionally, educational attainment and gender can be potential confounders. After controlling for these variables, there was no significant difference, nor was there any trend toward a difference, in the MDS-UPDRS motor examination or MoCA, our primary endpoints.