Exploratory imaging in SWEDD: Insights from dopaminergic PET, synaptic density PET, and volumetric MRI.

OBJECTIVE: Scans Without Evidence of Dopaminergic Deficit (SWEDD) refers to individuals with Parkinsonian symptoms but no presynaptic dopaminergic deficit on dopamine transporter (DAT) imaging. Given its likely heterogeneity, we used a multimodal imaging approach to compare SWEDD with Parkinson's disease (PD) and healthy controls (HCs). METHODS: Twenty participants with Parkinsonian symptoms (15 PD, 5 SWEDD) and 10 HCs underwent PET imaging with 18F-FE-PE2I (DAT) and 11C-UCB-J (SV2A), along with structural MRI. Binding potential (BPND) was quantified in striatal and midbrain regions. SWEDD classification was based on putamen DAT binding >80% of age-matched HCs. An exploratory sub-analysis compared SWEDD with early PD (disease duration <4 years). RESULTS: SWEDD showed higher putaminal DAT binding than PD (Z = 2.41, p = 0.01) but no difference from HCs (Z = 1.24, p = 0.21), indicating preserved nigrostriatal integrity. Unexpectedly, SWEDD had lower ventral striatum DAT binding versus HCs (Z = -2.79, p < 0.01). SV2A binding in the substantia nigra was higher in SWEDD than PD (Z = 2.33, p = 0.01), with no difference from HCs (Z = 0.49, p = 0.61), suggesting preserved synaptic density. Structural MRI showed no volumetric differences across groups. Clinically, SWEDD had lower MDS-UPDRS II, III, and total scores than PD, with similar MDS-UPDRS I scores. CONCLUSION: SWEDD demonstrated preserved dopaminergic and synaptic integrity compared with PD, without structural differences. Multimodal imaging may help characterize biological heterogeneity within SWEDD, though larger studies are needed.