Features of GBA-associated Parkinson’s disease at presentation in the UK Tracking Parkinson’s study

摘要: Objectives To examine the influence of glucocerebrosidase (GBA) mutation carrier state on age at onset Parkinson’s disease (PD), motor phenotype and cognitive function baseline assessment in a large cohort UK patients. We also analysed prevalence mood behavioural problems that may confound function. Methods prospectively recruited patients with PD Tracking study. fully sequenced GBA gene all recently diagnosed (≤3.5 years). examined (Montreal Cognitive Assessment) (Movement Disorder Society Unified Disease Rating Scale part 3) assessment, an average 1.3 years after diagnosis. used logistic regression to determine predictors mild impairment dementia. Results studied 1893 PD: 48 (2.5%) were heterozygous carriers for known Gaucher’s (GD) causing pathogenic mutations; 117 (6.2%) had non-synonymous variants, previously associated PD, 28 (1.5%) carried variants unknown significance gene. L444P was most common mutation. Patients mutations 5 younger compared non-carriers (P=0.02). GD-causing did not have increased family risk PD. more likely present postural instability gait difficulty carrying advanced Hoehn Yahr stage adjustment duration (P=0.005). There no differences between this early stage. Conclusions Our study confirms onset, severity Cognition differ baseline, implying impairment/dementia, reported other studies later stage, is cases. This offers important window opportunity potential disease-modifying therapy protect against development dementia GBA-PD.