Freezing of gait in Parkinson's disease with glucocerebrosidase mutations: prevalence, clinical correlates and effect on quality of life

Ruwei Ou; Chunyu Li; Qianqian Wei; Kuncheng Liu; Junyu Lin; Tianmi Yang; Yi Xiao; Qirui Jiang; Yangfan Cheng; Yanbing Hou; Lingyu Zhang; Wei Song; Xueping Chen; Xiaohui Lai; Huifang Shang

doi:10.3389/fnins.2023.1288631

Freezing of gait in Parkinson's disease with glucocerebrosidase mutations: prevalence, clinical correlates and effect on quality of life

Front Neurosci. 2023 Nov 28:17:1288631. doi: 10.3389/fnins.2023.1288631. eCollection 2023.

Authors

Affiliations

¹ Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Abstract

Objectives: Mutations in glucocerebrosidase (GBA1) can change the clinical phenotype of Parkinson's disease (PD). This study aimed to explore the clinical characteristics of freezing of gait (FOG) in PD patients with GBA1 mutations.

Methods: A whole-exome sequencing analysis was used to identify the GBA1 mutations (pathogenic or likely pathogenic) and exclude other PD-related gene mutations. A forward binary logistic regression model was conducted to identify the associated factors of FOG. The stepwise multiple linear regression analysis models were used to explore the effect of FOG on quality of life.

Results: The prevalence of FOG in patients with GBA1 mutations (30/95, 31.6%) was significantly higher than those in patients without GBA1 mutations (152/760, 20%) (p = 0.009). A higher (i.e., worse) Unified PD Rating Scale part III score (OR = 1.126, 95%CI = 1.061-1.194, p < 0.001) and a lower (i.e., worse) Montreal Cognitive Assessment score (OR = 0.830, 95%CI = 0.713-0.967, p = 0.017) were significantly associated with FOG in PD patients with GBA1 mutations. The presence of FOG was significantly associated with the decreased (i.e., worse) score of PD Questionnaire 39 after adjustment for sex, age, disease duration, motor score, and non-motor score (B = 14.981, p = 0.001).

Conclusion: FOG is a relatively common disabling symptom in PD patients with GBA1 mutations, which is affected by motor disability and cognitive decline. Quality of life is reduced in patients with FOG and GBA1 mutations.

Keywords: GBA1 mutation; Parkinson’s disease; freezing of gait; gene mutation; quality of life.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the funding of the National Science Fund of China (No. 82271272) and the Sichuan Science and Technology Program (No. 2022ZDZX0023).