Japanese journal of radiology · 2026
Dissociable associations of free-water fraction and DTI-ALPS index with disease manifestation and mutation carrier status in Parkinson's disease.
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Liu Chang, Liu Xi, Dong Meng, Li Wenze, Zhang Hongfa, Zhang Lu, Zhang Yuqing, Chen Yangmei
Аннотация
PURPOSE: Parkinson's disease (PD) is a biologically heterogeneous disorder. Diffusion MRI-derived free-water fraction (FWf) and DTI-ALPS index have been proposed as biomarkers of PD-related brain alterations; however, their relationships with clinical disease manifestation and genetic susceptibility remain unclear. This study investigated whether substantia nigra pars compacta (SNc) FWf and DTI-ALPS indices show different associations with disease status and mutation carrier status across the PD continuum.
MATERIALS AND METHODS: Diffusion MRI data from the Parkinson's Progression Markers Initiative were analyzed, including healthy controls (HCs), non-manifesting mutation carriers (NMCs), and patients with sporadic or genetic PD. A 2 × 2 factorial analysis of covariance was performed to assess the effects of disease status and mutation carrier status on SNc FWf and DTI-ALPS indices. Exploratory longitudinal associations between baseline imaging measures and 4-year clinical outcomes were examined using multivariable linear regression with adjustment for the corresponding baseline clinical measures.
RESULTS: Among 284 participants (63 HCs, 48 NMCs, 126 sporadic PD patients, and 47 genetic PD patients), mean SNc FWf showed a significant main effect of disease status, whereas mutation carrier status and the interaction effect were not significant. Sporadic PD patients exhibited higher SNc FWf than HCs and NMCs. In contrast, the left-sided DTI-ALPS index was associated with mutation carrier status. NMCs had lower left-sided DTI-ALPS indices than HCs and sporadic PD patients. In the exploratory longitudinal analysis, higher baseline mean SNc FWf was associated with a higher 4-year MDS-UPDRS Part II score, although this association was not significant when the analysis was restricted to participants with manifest PD.
CONCLUSIONS: SNc FWf and DTI-ALPS may capture complementary aspects of PD heterogeneity. SNc FWf appears more closely related to clinical disease expression, whereas DTI-ALPS index may reflect differences associated with genetic susceptibility. Further validation in larger mutation-stratified and longitudinal cohorts is warranted.
MATERIALS AND METHODS: Diffusion MRI data from the Parkinson's Progression Markers Initiative were analyzed, including healthy controls (HCs), non-manifesting mutation carriers (NMCs), and patients with sporadic or genetic PD. A 2 × 2 factorial analysis of covariance was performed to assess the effects of disease status and mutation carrier status on SNc FWf and DTI-ALPS indices. Exploratory longitudinal associations between baseline imaging measures and 4-year clinical outcomes were examined using multivariable linear regression with adjustment for the corresponding baseline clinical measures.
RESULTS: Among 284 participants (63 HCs, 48 NMCs, 126 sporadic PD patients, and 47 genetic PD patients), mean SNc FWf showed a significant main effect of disease status, whereas mutation carrier status and the interaction effect were not significant. Sporadic PD patients exhibited higher SNc FWf than HCs and NMCs. In contrast, the left-sided DTI-ALPS index was associated with mutation carrier status. NMCs had lower left-sided DTI-ALPS indices than HCs and sporadic PD patients. In the exploratory longitudinal analysis, higher baseline mean SNc FWf was associated with a higher 4-year MDS-UPDRS Part II score, although this association was not significant when the analysis was restricted to participants with manifest PD.
CONCLUSIONS: SNc FWf and DTI-ALPS may capture complementary aspects of PD heterogeneity. SNc FWf appears more closely related to clinical disease expression, whereas DTI-ALPS index may reflect differences associated with genetic susceptibility. Further validation in larger mutation-stratified and longitudinal cohorts is warranted.