The topography of brain damage at different stages of Parkinson's disease

Abstract

This study investigated gray matter (GM) and white matter (WM) damage in 89 patients at different clinical stages of Parkinson's disease (PD) (17 early, 46 mild, 14 moderate, and 12 severe) to differentiate the trajectories of tissue injury in this condition. PD patients had a very little GM atrophy even at the more advanced stages of the disease. Microstructural damage to the WM occurs with increasing PD severity and involves the brainstem, thalamocortical pathways, olfactory tracts, as well as the major interhemispheric, limbic, and extramotor association tracts. The most marked WM damage was found in moderate vs. mild cases. WM damage correlated with the degree of global cognitive deficits. WM abnormalities beyond the nigrostriatal system accumulate with increasing PD severity. WM damage is likely to contribute to the more severe motor and nonmotor dysfunctions occurring in patients at the later stages.

Keywords: DT MRI; Parkinson's disease; VBM; brain atrophy; white matter damage.

Figure 1

WM damage: whole‐brain analysis. Tract‐based spatial statistics results in moderate + severe PD patients vs. healthy controls (A) and early + mild PD patients (B). Voxelwise group differences are shown in blue (MD), red (FA), green (radD), and yellow (axD). Results are overlaid on the sagittal, coronal, and axial sections of the Montreal Neurological Institute standard brain in neurological convention (right is right) and displayed at P < 0.05, FWE corrected for multiple comparisons.

Figure 2

WM damage: ROI analysis. Tract‐based spatial statistics results in moderate vs. mild PD patients. Voxelwise group differences are shown in blue (MD), red (FA), and green (radD). Results are overlaid on the sagittal, coronal, and axial sections of the Montreal Neurological Institute standard brain in neurological convention (right is right) and displayed at P < 0.05, FWE corrected for multiple comparisons.

Figure 3

GM atrophy. (A) Whole‐brain analysis: areas of GM tissue loss in moderate + severe PD patients vs. healthy controls. (B) ROI analysis: areas of GM tissue loss in early PD patients vs. healthy controls and in moderate vs. mild PD patients. Results are superimposed on the sagittal, coronal, and axial sections of the Montreal Neurological Institute standard brain in neurological convention (right is right) and displayed at P < 0.05, FWE corrected for multiple comparisons.

Figure 4

WM damage vs. MMSE. Areas of WM tract damage associated with the MMSE scores in all PD patients. Voxelwise correlations are shown in red (FA). Results are overlaid on the sagittal, coronal, and axial sections of the Montreal Neurological Institute standard brain in neurological convention (right is right) and displayed at P < 0.05, FWE corrected for multiple comparisons.