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

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.