Objective: We explored [18F]FDG PET findings of PD patients with GBA mutation.

Background: Parkinson’s disease (PD) with glucocerebrosidase (GBA) mutations is characterized by early onset of disease and severe non-motor symptoms, such as cognitive impairment and neuropsychiatric disturbances. We recently reported significant hypometabolism in the posterior parietal cortex in PDD, and PD-MCI convertors to PDD

Method: Out of 105 PD patients screened(Centogene®), seven patients were found to have mutations in the GBA gene (PD-GBA, age=60.8±3.02 years, duration = 7.14±2.34 years). We then compared [18F]FDG PET findings of the PD-GBA group with other two PD groups: PD with long duration and normal cognition (PD-NC, n=18, age=66.2±2.54, Duration=14.1±2.8), and PD with dementia (PD-D, n=18, age=68.6±4.68, duration=7.17±5.10).

Results: All seven patients showed subnormal ß-glucerebrosidase activity(3.11±0.70, normal ≥ 4.1) with normal glucosylsphingosine(Lyso-Gb1, biomarker for Gaucher disease) levels. Parkinsonism at off state was severe in 4, moderate in 3 patients (UPDRS III =44.7±19.9). Cognition was normal in 6, mildly impaired in 1 patient (ACE-R=78.7±17.4). Six patients showed moderate depression (BDI=20.7±6.9) and apathy (AES-C=42.7±8.8, apathy≥31). Five patients showed impulse control disorder with drug-seeking, excessive hobbyism, or other compulsive behaviors. In the SPM analysis of [18F]FDG PET, the comparison of PD-GBA with healthy control showed significant hypometabolism in the dorsolateral prefrontal cortex, and posterior parietal cortex (p<0.05, FDR corrected) whereas the comparison with PD-NC showed significant hypometabolism in the posterior parietal cortex (p<0.05). In contrast, the comparison of PD-GBA with PD-D group did not show significant differences.

Conclusion: We found the mutation in GBA in seven out of 105 patients with sporadic PD with no evidence for Gaucher disease. All seven patients showed severe motor and non-motor symptoms. Our observations of [18F]FDG-PET in the PD-GBA group are similar to those in the PD-MCI convertors to PD-D. These findings are consistent with the view that the PD-GBA has a high risk of dementia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/significant-hypometabolism-in-the-posterior-parietal-cortex-and-precuneus-in-parkinsons-disease-with-gba-mutations-18ffdg-pet-study/