Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease

Abstract

Background and purpose: Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison.

Materials and methods: Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years.

Results: Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline (P < .001 and P = .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases (P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra.

Conclusions: Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known posterior-to-anterior substantia nigra degeneration that occurs over time in idiopathic Parkinson disease.

Fig 1.

Substantia nigra ROIs. Representative b=0 s/mm² images linearly registered to the MNI atlas are shown demonstrating the placement of the substantia nigra ROIs. Z-coordinates refer to the slice shown in MNI space. See the “Materials and Methods” section for a more detailed description of how ROIs were placed.

Fig 2.

Longitudinal changes in SN FW in patients with later-stage IPD and HCs. aSN and pSN FW group and group × time interaction intergroup differences were P < .001, = 0.021, and P = .014, = 0.651, respectively. Follow-up was approximately 3 years from baseline. Error bars are ± 1 standard error of mean.

Fig 3.

Change in the in bi-temporal lobe white matter FW-corrected mean diffusivity of subjects with IPD and corresponding changes in the MMSE and MoCA scores over 3 years. R² indicates coefficient of determination.