Objective: Using deformation-based morphometry (DBM) as a measure of atrophy, the aim of this study was to identify the regions presenting structural brain changes after four years in patients initially enrolled with de novo Parkinson’s disease (PD).

Background: Atrophy in multiple brain regions has been reported in PD even in the early stages (Zeighami et al., 2015). The progression of brain atrophy is still a matter of debate, however.

Method: Structural magnetic resonance images (T1-weighted MRI) and clinical data were obtained from the Parkinson’s Progression Markers Initiative (Marek et al., 2011), a multi-center database, for 79 PD patients (54 men, 25 women) with T1-weighted MRI at both baseline and four years, and 157 healthy control (HC; 103 men, 54 women) at baseline only. The structural MRI were converted to DBM maps using CAT12, a computational anatomy toolbox from SPM. The determinant of Jacobian matrix was calculated as the voxel-wise deformation value. A voxel-wise W-score map was computed for each patient with PD at baseline and four years to regress out the expected effects of age and sex (La Joie et al., 2012). Threshold-free cluster enhancement (TFCE) was computed using randomise, a FSL’s tool for nonparametric permutation inference on neuroimaging data (Winkler et al., 2014), to find clusters of significant difference between the W-score maps of the PD patients at baseline and four years. The results were controlled for the family-wise error (FWE) rate. A p-value less than 0.05 was considered significant.

Results: The TFCE analysis found four clusters showing greater atrophy at four years compared to baseline. The largest region was part of the left posterior cingulate gyrus (caudal area) while the second largest cluster was part of the left ventromedial putamen, ventral caudate, nucleus accumbens, and globus pallidus. Two smaller clusters including one in the right globus pallidus and in the right part of the midbrain also showed greater atrophy at four years.

Conclusion: This study showed that patients with de novo PD present brain atrophy progression after four years in specific regions. This is in line with Braak’s framework suggesting that Lewy body accumulation appears in the brainstem and spreads to subcortical and higher cortical areas as PD progresses (Braak et al. 2003).

References: Braak et al. (2003), ‘Staging of brain pathology related to sporadic Parkinson’s disease’, Neurobiol Aging, vol.24, 197-211. Marek K, et al. (2011), ‘The Parkinson Progression Marker Initiative (PPMI) ‘, Progress in Neurobiology, vol. 95, 629-635. Winkler AM et al. (2014), ‘Permutation inference for the general linear model’, Neuroimage, vol. 92, 381-397 Zeighami, Y et al. (2015), ‘Network structure of brain atrophy in de novo Parkinson’s disease’, Elife, vol. 4, e08440.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/brain-atrophy-progression-in-de-novo-parkinsons-disease/