Objective: We aimed to map the progression of cortical thinning and to test whether this pattern is constrained by network connectivity in the brain.

Background: It is hypothesized that neurodegenerative diseases such as Parkinson’s disease (PD) are caused by the cell-to-cell propagation of misfolded proteins. Evidence for this spreading model through the brain’s connectome predominantly comes from animal experiments whereas translational findings in humans remain largely limited. We used MRI-derived measures of cortical brain atrophy and connectivity maps to test this model in a large, longitudinal, and multicentre PD cohort.

Method: T1-weighted MRI scans of de novo PD patients at baseline, 1-, 2-, and 4-year follow-up and healthy controls at baseline were acquired from the Parkinson Progression Marker Initiative (PPMI). For each patient scan, we computed W-score maps to control for effects of normal aging, sex, and scanner site. We modeled longitudinal changes in cortical thickness across follow-up visits for the whole-brain as well as parcel-wise. To test the network spreading model, we calculated the amount of exposure each cortical region had to a defined subcortical ‘disease reservoir’ [1] using a PD-specific atrophy map measured at baseline [2] and connectivity maps generated from healthy subjects. Spearman’s correlation tested the relationship between cortical atrophy and degree of disease exposure.

Results: Mean whole-brain cortical thickness significantly decreased from baseline to 4-year follow-up. Parcel-wise analyses revealed regional atrophy in parietal, inferior temporal, paracentral gyrus, cingulate gyrus, and precuneus. Cortical thinning correlated with disease exposure, such that regions with greater exposure displayed greater atrophy.

Conclusion: Our results demonstrate a progressive pattern of cortical atrophy in early PD that is influenced by connectivity in the brain, lending support to a network spreading model.

References: [1] Yau, Y. et al. Network connectivity determines cortical thinning in early Parkinson’s disease progression. Nature Communications 9, 12 (2018). [2] Zeighami, Y. et al. Network structure of brain atrophy in de novo Parkinson’s disease. eLife 4, 1472 (2015).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-network-connectivity-in-shaping-the-progression-of-cortical-atrophy-in-parkinsons-disease/