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

Abstract

BackgroundDeep 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.MethodsParticipating 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.ResultsMD 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.ConclusionPallido-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.

Toward diffusion tensor imaging as a biomarker in neurodegenerative diseases: technical considerations to optimize recordings and data processing

“…For longitudinal studies in NDD with a rapidly progressive disease course, e.g., ALS, one baseline and two follow-up visits were advised over a total observation period of about 12 months (time interval between baseline and follow-up 2) to monitor the course of disease (e.g., Cardenas-Blanco et al, 2016 ; Kassubek et al, 2018 ; Kalra et al, 2020 ). For longitudinal studies in NDD with a slowly progressive disease course, multiple follow-up scans are possible and could even be spread over several years, e.g., in PD with one baseline and two follow-up visits 6 years apart ( Shih et al, 2023 ).…”

“…‣ PD [e.g., Gorges et al, 2019 – multicenter ( TIFT ); Zhang and Burock, 2020 – review; Shih et al, 2023 – monocenter (FSL)].…”

“…Previous studies that analyzed longitudinal alterations in ALS patients ( Zhang et al, 2016 ; Kassubek et al, 2018 ; Kalra et al, 2020 ; Shih et al, 2023 ) calculated the effect size of longitudinal differences in a given DTI metric by…”