Dual‐phase 18F‐FP‐CIT positron emission tomography and cardiac 123I‐MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body‐first type?

Abstract Background and purpose Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA‐PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta‐iodobenzylguanidine (MIBG) uptake of GBA‐PD in comparison to sPD. Methods Through next‐generation sequencing analysis targeting 41 genes, a total of 16 GBA‐PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual‐phase [18F]‐N‐(3‐fluoropropyl)‐2β‐carboxymethoxy‐3β‐(4‐iodophenyl) nortropane (18F‐FP‐CIT) positron emission tomography (PET) and cardiac 123I‐MIBG scintigraphy results were compared between the two groups. Results The GBA‐PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early‐phase 18F‐FP‐CIT PET showed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p = 0.011) and part of the occipital cortex (p < 0.05) in the GBA‐PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate‐to‐putamen ratio were similar between the two groups. The GBA‐PD group had a lower heart‐to‐mediastinum uptake ratio in 123I‐MIBG scintigraphy than the sPD group. Conclusions The GBA‐PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non‐motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA‐PD than sPD. These findings suggest that GBA‐PD patients have more widespread peripheral (extranigral) α‐synuclein accumulation, representing a body‐first PD subtype.