Category: Parkinson's disease: Neuroimaging
Objective: To investigate dopaminergic and synaptic density in SWEDD patients compared to idiopathic Parkinson’s disease (IPD) and healthy controls (HCs).
Background: Scans Without Evidence of Dopaminergic Deficit (SWEDD) describe clinical parkinsonism but with normal dopamine transporter imaging. Most SWEDD subjects have reported [¹²³I]FP-CIT uptake ratios, but [¹⁸F]FE-PE2I PET has higher resolution and more sensitivity to detect differences. Additionally, [¹¹C]UCB-J PET, a marker of synaptic density, provides insights into neurodegeneration beyond dopamine dysfunction.
Method: Twenty clinically diagnosed PD subjects (9 men; age: 62.9 ± 6.2 years) and ten HCs (6 men; age: 59.9 ± 3.7 years) underwent PET scans with [¹⁸F]FE-PE2I and [¹¹C]UCB-J PET. Binding potential (BPND) values were quantified in the caudate, putamen, and substantia nigra (SN), with references in the cerebellum ([¹⁸F]FE-PE2I) and centrum semiovale ([¹¹C]UCB-J). Four SWEDD subjects were identified based on putamen [¹⁸F]FE-PE2I BPND ratios exceeding 80% of the age-matched HC mean value.(1)
Results: SWEDD subjects had a putamen [¹⁸F]FE-PE2I ratio between 82–91%, the remaining IPD group had ratios below 50%. For [¹⁸F]FE-PE2I, SWEDD subjects showed 13% lower putamen values vs. HCs and 64% higher vs. IPD (both p < 0.05). The SN was 5% lower vs. HCs and 22% higher vs. IPD, while the caudate was by 29% lower vs. HCs and 32% higher vs. IPD (non-significant). For [¹¹C]UCB-J, SWEDD showed 23% and 10% lower BPND in caudate and putamen vs. HCs and 6% and 27% lower compared to IPD. Interesting, there was 17% higher binding in the SN vs. IPD and 3% higher vs. HCs (non-significant).
Conclusion: This is the first study to assess SWEDD with [¹⁸F]FE-PE2I and [¹¹C]UCB-J PET. In this small sample, SWEDD subjects showed dopamine values between HC and IPD and non-significant lower synaptic density compared to both HC and IPD, with the exception of the SN. This suggests involvement of non-dopaminergic mechanisms.
References: Marek K, Seibyl J, Eberly S, Oakes D, Shoulson I, Lang AE, Hyson C, Jennings D, Parkinson Study Group PRECEPT Investigators. Longitudinal follow-up of SWEDD subjects in the PRECEPT Study. Neurology. 2014 May 20;82(20):1791-7.
To cite this abstract in AMA style:
F. Ebrahimian Sadabad, T. Volpi, P. Honhar, L. Colon, S. Tinaz, M. Naganawa, M. Dias, G. Angarita, R. Comley, R. Carson, S. Finnema, D. Matuskey. Dopaminergic and Synaptic Alterations in SWEDD: Insights from [¹⁸F] FE-PE2I and [¹¹C] UCB-J PET Imaging [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/dopaminergic-and-synaptic-alterations-in-swedd-insights-from-%c2%b9%e2%81%b8f-fe-pe2i-and-%c2%b9%c2%b9c-ucb-j-pet-imaging/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/dopaminergic-and-synaptic-alterations-in-swedd-insights-from-%c2%b9%e2%81%b8f-fe-pe2i-and-%c2%b9%c2%b9c-ucb-j-pet-imaging/