Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Parkinson's disease involves alpha-synuclein aggregates, but their origin is unclear.
• Hypothesized subtypes: brain-first (originating in the brain) and body-first (originating in the peripheral nervous system).
• Isolated REM sleep behavior disorder (iRBD) may precede the body-first subtype.

Purpose of the Study:

• To investigate the hypothesized brain-first and body-first subtypes of Parkinson's disease.
• To differentiate subtypes using multimodal imaging of neuronal dysfunction.
• To assess the role of iRBD as a prodromal marker for the body-first type.

Main Methods:

• Case-control PET study with 37 de novo Parkinson's disease patients (RBD-negative and RBD-positive) and 22 iRBD patients.
• Utilized 11C-donepezil PET/CT (cholinergic innervation), 123I-MIBG scintigraphy (cardiac sympathetic innervation), neuromelanin-sensitive MRI (locus coeruleus), and 18F-FDOPA PET (dopamine storage).
• Assessed colon volume and transit times using CT and radiopaque markers.

Main Results:

• Parkinson's disease patients (both RBD-negative and RBD-positive) showed reduced putaminal FDOPA uptake; iRBD patients mostly had normal scans.
• RBD-positive and iRBD patients exhibited reduced cardiac MIBG and colon 11C-donepezil uptake compared to RBD-negative patients.
• RBD-positive patients showed enlarged colon volumes and delayed transit times, suggesting a body-first trajectory.

Conclusions:

• Findings support distinct brain-first and body-first subtypes of Parkinson's disease.
• The body-first subtype is characterized by initial peripheral autonomic and enteric nervous system dysfunction.
• iRBD may serve as a prodromal phenotype for the body-first Parkinson's disease subtype.