Dopaminergic Dysfunction Is More Symmetric in Dementia with Lewy Bodies Compared to Parkinson's Disease

Background: The alpha-syn Origin site and Connectome model (SOC) proposes that alpha-synucleinopathies can be divided into two categories: the asymmetrical brain-first, and more symmetrical body-first Lewy body disease. We have hypothesized that most patients with dementia with Lewy bodies (DLB) belong to the body-first subtype, whereas patients with Parkinson's disease (PD) more often belong to the brain-first subtype. Objective: To compare asymmetry of striatal dopaminergic dysfunction inDLBandPDpatients using [18F]-FE-PE2I positron emission tomography (PET). Methods: We analyzed [F-18]-FE-PE2I PET data from 29 DLB patients and 76 PD patients who were identified retrospectively during a 5-year period at Dept. of Neurology, Aarhus University Hospital. Additionally, imaging data from 34 healthy controls was used for age-correction and visual comparison. Results: PD patients showed significantly more asymmetry in specific binding ratios between the most and least affected putamen (p < 0.0001) and caudate (p = 0.003) compared to DLB patients. PD patients also had more severe degeneration in the putamen compared to the caudate in comparison to DLB patients (p < 0.0001) who had a more universal pattern of striatal degeneration. Conclusion: Patients with DLB showsignificantly more symmetric striatal degeneration on average compared to PD patients. These results support the hypothesis that DLB patients may be more likely to conform to the body-first subtype characterized by a symmetrical spread of pathology, whereas PD patients may be more likely to conform to the brain-first subtype with more lateralized initial propagation of pathology.

Automated summary

The study compared the striatal dopaminergic dysfunction asymmetry between patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD). It found that DLB patients had more symmetric striatal degeneration compared to PD patients, which supports the hypothesis that DLB patients may conform to the body-first subtype while PD patients may conform to the brain-first subtype.