Objective: To explore the regional cholinergic innervation and clinical profile of early Parkinson’s disease (PD) patients carrying GBA mutations (GBA-PD).

Background: The most common genetic risk factors for PD are mutations of the GBA1-gene (GBA), encoding for the lysosomal enzyme glucocerebrosidase (GCase). GBA-PD is characterized by a worse clinical prognosis with faster disease progression, more severe cognitive impairment, mood disorders, postural instability and gait problems. A rapid degeneration of the cholinergic system might contribute to explaining the GBA-related phenotype. Vesicular acetylcholine transporter (VAChT) PET imaging provides the opportunity to investigate regional cholinergic innervation and its relationship with clinical symptomatology.

Method: 40 GBA and 92 non-GBA early PD patients were included in the Dutch Parkinson Cohort (DUPARC), supplemented with known GBA-PD patients of a nation-wide Dutch GBA Cohort. Assessments included MDS-UPDRS part II, III and IV, levodopa equivalent daily dose (LEDD) and an extensive neuropsychological assessment. Non-motor symptoms were evaluated via the Non-Motor Symptom Questionnaire (NMSQ), the Hospital Anxiety and Depression Scale, the REM sleep Behaviour Disorder Screening Questionnaire, and the Sniffin’ Sticks olfactory test. Differences in cholinergic innervation between GBA carriers and non-carriers were assessed by PET imaging using the VAChT tracer [¹⁸F]fluoroethoxybenzovesamicol, using a voxel-wise and region of interest (ROIs)-based approach.

Results: GBA-PD (24 males (60.0%), mean (SD) age 68.3 (7.4), median [Q1-Q3]) disease duration 58 months [37.3-73.8]) presented with significantly higher LEDD, UPDRS IV, and total NMSQ compared to non-GBA PD (70 males (76.1%), mean age 67.0 (8.6), median disease duration; 36 months [35-37]). No significant differences in motor and non-motor symptoms were found between both groups correcting for disease duration. The cognitive profiles of GBA-PD and non-GBA PD will be shown. In addition, the difference in cholinergic innervation topography corrected for disease duration between both groups will be shown.

Conclusion: Our clinical data align with the previous literature: GBA and non-GBA PD are almost clinically indistinguishable at the onset of symptoms. This study provides the opportunity to investigate the cholinergic neuro-imaging status and its relationship with clinical symptomatology in early GBA-PD patients.

References: Boertien, J.M., van der Zee, S., Chrysou, A. et al. Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson’s disease patients for the identification and validation of biomarkers for Parkinson’s disease subtypes, progression and pathophysiology. BMC Neurol 20, 245 (2020).

den Heijer JM, Cullen VC, Quadri M, Schmitz A, Hilt DC, Lansbury P, Berendse HW, van de Berg WDJ, de Bie RMA, Boertien JM, Boon AJW, Contarino MF, van Hilten JJ, Hoff JI, van Mierlo T, Munts AG, van der Plas AA, Ponsen MM, Baas F, Majoor-Krakauer D, Bonifati V, van Laar T, Groeneveld GJ. A Large-Scale Full GBA1 Gene Screening in Parkinson’s Disease in the Netherlands. Mov Disord. 2020 Sep;35(9):1667-1674.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/cholinergic-topography-and-clinical-profile-of-early-parkinsons-patients-with-gba-mutations/