Amygdala neurodegeneration differentiates brain-first and body-first Parkinson's disease: An MRI study

Two distinct patterns of alpha-synuclein spread in Parkinson's disease were proposed with a body-first and a brain-first subtype. The body-first subtype originates in the periphery, while the brain-first subtype initiates in the central nervous system, notably affecting the amygdala. This retrospective cross-sectional study compared the integrity of the substantia nigra and amygdala between body-first and brain-first Parkinson's disease subtypes. We analyzed data from 30 Parkinson's disease patients, classified into body-first (n = 21) and brain-first (n = 9) subtypes based on REM sleep behavior disorder history. Microstructural integrity was assessed using diffusion microstructure MRI. No significant differences were found in the substantia nigra between subtypes. However, amygdala degeneration was significantly pronounced in the "brain-first" compared to the "body-first" group reflected by increased free interstitial fluid (p = 0.02, Cohen's d = -1.22). The degeneration of amygdala is distinctively pronounced in "brain-first" Parkinson's disease, supporting differential disease progression patterns between subtypes.