Objective: To investigate the longitudinal relationship between changes in dopamine transporter single-photon emission computed tomography (DaT SPECT) and changes in motor symptom severity in Parkinson’s disease (PD). We aimed to provide a potential model to test the efficiency of disease-modifying drugs aiming at the maintenance or rescue of dopaminergic neurons.

Background: The value of DaT SPECT as a monitoring biomarker in PD is under debate. Previously, longitudinal changes in DaT SPECT and in motor symptom severity, as measured by the Unified Parkinson’s Disease Rating Scale motor part (UPDRS III) were reported to not correlate [1]. We hypothesized that the relationship between DaT SPECT and UPDRS III changes is much stronger, when the less affected putamen and the contralateral increase in akinetic-rigid motor symptoms is compared.

Method: Longitudinal (four-year follow-up) imaging and clinical data of 558 patients with PD were obtained from the Parkinson’s Progression Initiative (PPMI) database. The resulting 1581 data points were entered in a linear mixed model. Longitudinal dopamine transporter availability, time, and the interaction (dopamine transporter signal*time) were used as primary predictors to model the increase in motor symptoms. To account for the repeated measure design, we allowed random intercepts and slopes regarding individual subjects and time.

Results: We observed a significant association between the decrease in the less affected putaminal DaT SPECT signal and motor symptom increase in the contralateral bodyside.

Conclusion: It is possible to show a significant longitudinal relationship between dopamine transporter availability and motor symptoms in a mixed model. This model might be of value for clinical trials evaluating the potential of drugs delaying dopaminergic degeneration.

References: [1] Simuni T, Siderowf A, Lasch S, Coffey CS, Caspell-Garcia C, Jennings D, Tanner CM, Trojanowski JQ, Shaw LM, Seibyl J, Schuff N, Singleton A, Kieburtz K, Toga AW, Mollenhauer B, Galasko D, Chahine LM, Weintraub D, Foroud T, Tosun D, Poston K, Arnedo V, Frasier M, Sherer T, Chowdhury S, Marek K; Parkinson’s Progression Marker Initiative*. Longitudinal Change of Clinical and Biological Measures in Early Parkinson’s Disease: Parkinson’s Progression Markers Initiative Cohort. Mov Disord. 2018 May;33(5):771-782. doi: 10.1002/mds.27361.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-transporter-imaging-as-monitoring-biomarker-in-parkinsons-disease/