Differential cholinergic white matter microstructural alterations in multiple system atrophy and Parkinson's disease.

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BackgroundMultiple system atrophy (MSA) and Parkinson's disease (PD) are both α-synucleinopathies with distinct pathological features and disease courses. MSA is characterized by more extensive white matter damage and widespread cortical and subcortical cholinergic systems degeneration than PD. However, the extent and pattern of microstructural alterations of cholinergic pathways in MSA and PD remain unclear.MethodWe included 30 patients with MSA, 253 patients with PD and 46 sex- and age-matched healthy controls (HC). Probabilistic tractography was used to construct two major cholinergic pathways: from the nucleus basalis of Meynert (NBM) to cortex and from the pedunculopontine nucleus (PPN) to thalamus. Free water (FW) imaging was applied to evaluate microstructural alterations in these pathways as well as NBM and PPN. Voxel-wise analyses were assessed on localized microstructural changes and spatial heterogeneity, and receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory power in differentiating MSA from PD.ResultMSA exhibited significantly higher FW in the PPN-thalamus, NBM-external capsule, and NBM-cingulum pathways compared to both PD and HC groups (all p ConclusionThe PPN-thalamus pathway showed the most prominent FW increase in MSA, suggesting its selective vulnerability and potential for aiding the differential diagnosis between MSA and PD. Moreover, distinct patterns of microstructural alterations highlight the spatial heterogeneity of cholinergic degeneration across α-synucleinopathies.

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