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

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).

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 (BP_ND) 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).

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.

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.