Serial deep gray nuclear DTI changes in Parkinson's disease over twelve years

Abstract

Background: Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson's disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years.

Methods: Participating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time.

Results: MD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores.

Conclusion: Pallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.

Keywords: Parkinson’s disease; basal ganglia; diffusion tensor imaging (DTI); longitudinal; neurodegeneration.

FIGURE 1

Temporal fractional anisotropy (FA) (A,B) and mean diffusivity (MD) (C,D) profiles in the four deep gray nuclei across 12 years. The profiles in rows (A,C) were obtained from all participants in the full cohort, whereas the profiles in the rows (B,D) were obtained from the subset cohort who completed all three-timepoint MRI examinations. The blue solid line indicates mean DTI metrics in healthy controls, whereas the red dotted line indicates mean DTI metrics in PD patients. Although between-group comparisons using the subset cohort dataset show marginal FA differences (uncorrected-p < 0.05) in the thalamus at the second timepoint and globus pallidus at the third timepoint (B), the overall longitudinal DTI changes in all nuclei from both the full and subset cohorts are remarkably similar, indicating little censoring effect from subject dropout and/or incongruent sample sizes across 12 years in our results of the full cohort data. (E) Color coded labels of the four deep gray nuclear regions of interest (ROI) as defined in the Montreal Neurological Institute (MNI) 152 T1-weighted template.

FIGURE 2

Results of Partial Pearson correlation analysis with adjustments for age, gender and levodopa equivalent dose. Correlations of disease duration with mean diffusivity of the four deep gray nuclei (caudate, putamen, globus pallidus, and thalamus) provided by the panel (A) full and (B) subset cohort data across 12 years.