Objective: We sought to validate cortical thickness as an objective biomarker of Parkinson’s disease (PD) progression.

Background: Cortical thickness analysis has been proposed as a more sensitive measure of age- and disease-related changes in cortical integrity than voxel-based morphometry [1]. The application of this technique in PD progression has yielded inconsistent findings, however [2]. This discrepancy is explained by studies with small patient samples and cross-sectional designs that fail to account for disease heterogeneity.

Method: In the present study, we investigated the trajectory of cortical thinning in a large, longitudinal, and multicentre cohort of PD patients. T1-weighted MRI scans of de novo PD patients from the Parkinson Progression Marker Initiative (PPMI) were acquired at baseline, 1-, 2-, and 4-year follow-up. For each scan, we computed a W-score map to control for age-related changes. We modeled longitudinal changes in cortical thickness across time points, covaried with age and sex.

Results: One-year post-diagnosis, early regional thinning was observed in the left inferior frontal lobe, left temporal pole, and right somatomotor cortex. By 2-year follow-up, cortical atrophy had become relatively widespread. Mean whole-brain cortical thickness significantly decreased from baseline (3.248mm±0.011) to 2-years (3.220mm±0.010), however this early atrophy appeared to plateau by 4-year follow-up (3.218mm±0.010). PD patients showed early regional thinning in frontal and parietal areas, replicating earlier findings. This cortical atrophy continued to rapidly spread before appearing to level off in a non-linear trajectory.

Conclusion: PD patients showed early regional thinning in frontal and parietal areas, replicating earlier findings [3]. This cortical atrophy continued to rapidly spread before appearing to level off in a non-linear trajectory. Our results demonstrate the use of cortical atrophy as a potential biomarker for PD and PD progression.

References: [1] Pereira, J. B. et al. (2012), ‘Assessment of cortical degeneration in patients with Parkinson’s disease by voxel-based morphometry, cortical folding, and cortical thickness’, Human Brain Mapping, vol. 33, pp. 2521– 2534 [2] Yang, J. et al. (2018), ‘Longitudinal Progression Markers of Parkinson’s Disease: Current View on Structural Imaging’, Current Neurology and Neuroscience Reports, vol. 18, no. 12, pp. 83 [3] Yau, Y. et al. (2018), ‘Network connectivity determines cortical thinning in early Parkinson’s disease progression’, Nature Communications, vol. 9, no. 1, pp. 12

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