AUTHOR=Ren Jingru , Zhou Gaiyan , Wang Yajie , Zhang Ronggui , Guo Zhiying , Zhou Hao , Zheng Huifen , Sun Yu , Ma Changyan , Lu Ming , Liu Weiguo 

TITLE=Association of GBA genotype with motor and cognitive decline in Chinese Parkinson’s disease patients

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1091919

DOI=10.3389/fnagi.2023.1091919

ISSN=1663-4365

ABSTRACT=<sec><title>Objective</title><p>Variants in the glucocerebrosidase (<italic>GBA</italic>) gene are the most common and significant risk factor for Parkinson’s disease (PD). However, the impact of <italic>GBA</italic> variants on PD disease progression in the Chinese population remains unclear. This study aimed to explore the significance of <italic>GBA</italic> status on motor and cognitive impairment in a longitudinal cohort of Chinese patients with PD.</p></sec><sec><title>Methods</title><p>The entire <italic>GBA</italic> gene was screened by long-range polymerase chain reaction (LR-PCR) and next generation sequencing (NGS). A total of 43 <italic>GBA</italic>-related PD (<italic>GBA</italic>-PD) and 246 non-<italic>GBA</italic>-mutated PD (NM-PD) patients with complete clinical data at baseline and at least one follow-up were recruited for this study. The associations of <italic>GBA</italic> genotype with rate of motor and cognitive decline, as measured by Unified PD Rating Scale (UPDRS) motor and Montreal Cognitive Assessment (MoCA), were assessed by linear mixed-effect models.</p></sec><sec><title>Results</title><p>The estimated (standard error, SE) UPDRS motor [2.25 (0.38) points/year] and MoCA [−0.53 (0.11) points/year] progression rates in the <italic>GBA</italic>-PD group were significantly faster than those in the NM-PD group [1.35 (0.19); −0.29 (0.04) points/year; respectively]. In addition, the <italic>GBA</italic>-PD group showed significantly faster estimated (SE) bradykinesia [1.04 (0.18) points/year], axial impairment [0.38 (0.07) points/year], and visuospatial/executive [−0.15 (0.03) points/year] progression rates than the NM-PD group [0.62 (0.10); 0.17 (0.04); −0.07 (0.01) points/year; respectively].</p></sec><sec><title>Conclusion</title><p><italic>GBA</italic>-PD is associated with faster motor and cognitive decline, specifically greater disability in terms of bradykinesia, axial impairment, and visuospatial/executive function. Better understanding of <italic>GBA</italic>-PD progression may help predict prognosis and improve clinical trial design.</p></sec>