Central Involvement in Pure Autonomic Failure: Insights from Neuromelanin-Sensitive Magnetic Resonance Imaging and 18F-Fluorodopa-Positron Emission Tomography

Central synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies.BACKGROUNDCentral synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies.To assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients.OBJECTIVESTo assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients.Participants with PAF (n = 23) were categorized as high-LR (n = 13) or low-LR (n = 10) for conversion to central synucleinopathy. Additional participants included PD (n = 22), DLB (n = 8), and age- and sex-matched healthy controls (n = 23). NM-MRI at 3 T was used to quantify contrast ratios in the LC and SN, while FDOPA-PET measured presynaptic dopamine synthesis. Linear regression analyses, adjusted for age and sex, were used to compare NM-MRI contrast across groups.METHODSParticipants with PAF (n = 23) were categorized as high-LR (n = 13) or low-LR (n = 10) for conversion to central synucleinopathy. Additional participants included PD (n = 22), DLB (n = 8), and age- and sex-matched healthy controls (n = 23). NM-MRI at 3 T was used to quantify contrast ratios in the LC and SN, while FDOPA-PET measured presynaptic dopamine synthesis. Linear regression analyses, adjusted for age and sex, were used to compare NM-MRI contrast across groups.High-LR PAF patients showed reduced contrast in the LC and SN compared with controls