Longitudinal dual-tracer PET study reveals early frontal cholinergic loss in GBA1-variant Parkinson’s disease, highlighting targeted pathways for cognitive decline.
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, 18 F-fluoroethoxy-benzovesamicol ( 18 F-FEOBV) PET (cholinergic) and 3,4-dihydroxy-6- 18 F-fluoro-I-phenylalanine ( 18 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 18 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 18 F-FEOBV PET as biomarker.
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Slingerland et al. (2025) studied this question.
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