Objective: To investigate the longitudinal course of nigrostriatal metabolic and dopaminergic dysfunction and its impact on symptom severity in Parkinson’s disease (PD) patients using a multi-tracer PET study.

Background: The progressive course of neuropathology in an ascending fashion was first introduced by Braak et al. and gave rise to the current prevailing network perspective on PD pathology[1]. In this context, we recently identified a hypometabolic midbrain cluster and concomitant dopaminergic putaminal degeneration in PD patients in a multi-tracer PET study[2]. Further, we were able to assign both findings to motor disability. This study aimed to validate our previous results longitudinally on a subgroup of patients from the same cohort receiving multimodal follow-up (FU) examinations.

Method: We evaluated the progression of nigrostriatal deficits and their relation to increasing disease severity in 16 clinically well-characterized PD patients undergoing ¹⁸F-FDG-PET, ¹⁸F-DOPA-PET at two consecutive visits (mean interval of about 14 months) along with 14 healthy control subjects (HC). Whole-brain group comparisons of PET Scans with small volume corrections for bilateral midbrain and striatum were performed as paired- and two-sample-t-tests among BL and FU visit scans or with respect to HC, respectively. We further ascertained correlations between imaging findings and clinical scores with repeated-measures-ANCOVA[3].

Results: At FU visit, ¹⁸F-FDG metabolism in the left midbrain decreased along with ¹⁸F-DOPA-uptake in the right caudate. Both measures of nigrostriatal dysfunction at the FU visit were positively correlated (r = 0.667, p= 0.005). Compared to HC, we additionally detected reduced ¹⁸F-FDG metabolism in the right midbrain in the FU-cohort. Further, progression in reduced tracer uptakes was related to worsening in left body motor scores and increase in disease duration.

Conclusion: By applying a multimodal PET-imaging approach to a well-characterized PD cohort, we documented for the first time an interrelation between progressive striatal dopaminergic dysfunction and midbrain hypometabolism, that both were associated with clinical deterioration. Our findings underline the benefit of multimodal high-resolution PET imaging in detecting nigrostriatal pathway dysfunction in PD patients and shed new light on the functional pathomechanisms and network-dependent degeneration underlying disease progression.

References: 1. Braak, H. et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging 24, 197–211 (2003). 2. Ruppert, M. C. et al. Network degeneration in Parkinson’s disease: multimodal imaging of nigro-striato-cortical dysfunction. Brain 143, 944–959 (2020). 3. Bakdash, J. Z. & Marusich, L. R. Repeated measures correlation. Front. Psychol. 8, 1–13 (2017).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/progression-of-nigrostriatal-dysfunction-in-parkinsons-disease-a-longitudinal-multimodal-pet-study/