Publication date: Nov 12, 2025
Parkinson’s Disease (PD) patients carrying GBA1-variants (GBA-PD) often show a faster cognitive decline, suggesting accelerated cholinergic degeneration. This study investigated changes over time in whole-brain cholinergic innervation within the context of dopaminergic changes and clinical outcomes in GBA-PD versus non-GBA-PD. 171 PD participants (44 GBA-PD, 127 non-GBA-PD) underwent clinical and neuropsychological assessments, brain MRI, F-fluoroethoxy-benzovesamicol (F-FEOBV) PET (cholinergic) and 3,4-dihydroxy-6-F-fluoro-I-phenylalanine (F-FDOPA) PET (dopaminergic) imaging. GBA-PD participants showed worse executive functioning than non-GBA-PD. Voxel-wise linear mixed-effects models showed that GBA-PD exhibited lower F-FEOBV binding in the right precentral and middle frontal gyrus, independent of age and sex, despite similar cholinergic decline over time. No GBA1-related differences were found in dopaminergic signal or its progression. Age and time since diagnosis were associated with progressive cholinergic and dopaminergic denervation in all patients. This first dual-tracer longitudinal PET study highlights early cholinergic involvement in GBA-PD and supports further evaluation of F-FEOBV PET as biomarker.
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| Concepts | Keywords |
|---|---|
| Benzovesamicol | Brain |
| Biomarker | Cholinergic |
| Faster | Clinical |
| Gba1 | Decline |
| Parkinsons | Dopaminergic |
| Feobv | |
| Gba | |
| Gba1 | |
| Imaging | |
| Parkinson | |
| Participants | |
| Pd | |
| Pet | |
| Variants |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Parkinson’s disease |
| disease | MESH | cognitive decline |
| drug | DRUGBANK | L-Phenylalanine |
| disease | MESH | dementia |
| drug | DRUGBANK | Acetylcholine |
| drug | DRUGBANK | Coenzyme M |