Clinical and Dopamine Transporter Imaging Trajectories in a Cohort of Parkinson's Disease Patients with GBA Mutations

Background Glucosylceramidase (GBA) mutations are considered the most common genetic risk factors for developing Parkinson's disease (PD). Objectives We aimed to assess, at different time points, the integrity of brain striatal and extra-striatal dopamine pathways and clinical phenotype of a group of PD subjects bearing heterozygous GBA mutations (GBA-PD), compared with a group of idiopathic PD patients (iPD) stratified by age at disease onset. A longitudinal approach was adopted to evaluate the progression over time for clinical and I-123-FP-CIT SPECT imaging features. Methods We considered 46 GBA-PD patients and 339 iPD patients, subdivided into two groups according to age at PD onset (n = 58 < 50 years and n = 281 > 50 years). We measured differences in the occurrence/severity/progression of motor and non-motor features, I-123-FP-CIT standard uptake value ratios (SUVr) in striatal and extra-striatal regions, and global cognitive deterioration over time in a subset of 168 cases with available follow-up. Results At baseline, the GBA-PD cohort showed more severe motor and cognitive deficits than the early-iPD cohort. The I-123-FP-CIT SUVr reduction in the striatal and the extra-striatal regions was more marked in the GBA-PD than the early- and late-iPD cohorts. Both GBA-PD and late-iPD patients had a significant annual deterioration in their global cognitive performance, while the early-iPD group showed global cognitive stability over time. At follow-up, the iPD cohorts became similar to the GBA-PD group in I-123-FP-CIT SUVr reduction. Conclusion These new findings support the hypothesis of a biological role of GBA mutations in accelerating the early neurodegenerative processes in PD, leading to the malignant clinical phenotype. (c) 2021 International Parkinson and Movement Disorder Society

Automated summary

The study demonstrates that PD patients with GBA mutations show more severe deficits in cognition and motor function, with more significant damage in the striatal and extra-striatal regions observed on I-123-FP-CIT imaging. Both GBA-PD and late-iPD patients exhibit global cognitive deterioration, while the early-iPD group maintains cognitive stability over time. Over the course of follow-up, the iPD cohorts show a similar reduction in I-123-FP-CIT SUVr to the GBA-PD group.