Long-term trends in myocardial sympathetic innervation and function in synucleinopathies

Abstract

IntroductionParkinson disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA) are characterized by intra-cerebral deposition of the protein alpha-synuclein and are termed synucleinopathies. Lewy body synucleinopathies involve decreased cardiac sympathetic innervation and functional abnormalities in residual noradrenergic terminals. This observational, retrospective, cohort study describes long-term trends in indices of cardiac sympathetic innervation and function in synucleinopathies. MethodsPatients with PD (N = 31), PAF (N = 9), or MSA (N = 9) underwent repeated 18F-dopamine positron emission tomography (median follow-up 3.5 years). Interventricular septal 18F-dopamine-derived radioactivity 8 min after tracer injection (8′ Radioactivity) was used as an index of sympathetic innervation and the slope of mono-exponential decline of radioactivity between 8 and 25 min (k8’-25’) as an index of intraneuronal vesicular storage. Healthy volunteers (HVs) (N = 33) and individuals at high risk of PD (N = 15) were controls. ResultsUpon initial evaluation the groups with PD and orthostatic hypotension (OH), PAF, or PD and no OH had low mean 8′ Radioactivity compared to HVs (p < 0.0001, p = 0.0002, p = 0.006) and had elevated k8’-25’ (p = 0.0007, p = 0.007, p = 0.06). There was no significant difference between MSA and HVs. In PD 8′ Radioactivity decreased by a median of 4% per year and did not decrease in MSA. k8’-25’ values did not change during follow-up in any group. ConclusionsNeuroimaging evidence of decreased vesicular uptake in cardiac sympathetic nerves is present upon initial evaluation of patients with Lewy body synucleinopathies and may provide a biomarker of catecholaminergic dysfunction early in the disease process.