Gray matter atrophy distinguishes between Parkinson disease motor subtypes

Abstract

Objective: To assess differences in gray matter (GM) atrophy between 2 Parkinson disease (PD) subtypes: the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype.

Methods: Patients were classified as belonging to the predominately PIGD (n = 30) or predominately TD (n = 29) subtype. Voxel-based morphometry was used to compare GM in these 2 subtypes and to evaluate correlations between predefined regions of interest and the degree of symptoms. In the regions where GM atrophy was associated with symptoms, the relationship between GM volumes and functional connectivity was examined.

Results: GM was reduced in the predominately PIGD group, compared with the predominately TD group, in areas that involve motor, cognitive, limbic, and associative functions (p < 0.05, false discovery rate corrected). Lower GM volumes in the pre-supplementary motor area (SMA) and in the primary motor area were associated with increased severity of PIGD symptoms (r = -0.42, p < 0.001; r = -0.38, p < 0.003, respectively). Higher GM volumes within the pre-SMA were associated with stronger functional connectivity between the pre-SMA and the putamen (r = 0.415, p < 0.025) in the patients with predominately PIGD.

Conclusions: In patients with PD, PIGD symptoms are apparently associated with GM atrophy in motor-related regions and decreased functional connectivity. GM degeneration and a related decrease in spontaneous coactivation between cortical and subcortical motor-planning areas may partially account for the unique clinical characteristics of a subset of patients with PD.

Figure 1. Areas of gray matter atrophy derived from a voxel-based morphometric direct comparison between patients with p-TD (n = 29) and p-PIGD (n = 30) subtypes

The results are superimposed in representative sagittal and axial sections of a customized gray matter template, at a threshold of p < 0.05, false discovery rate corrected. IFG = inferior frontal gyrus; IPL = inferior parietal lobe; PHG = parahippocampal gyrus; p-PIGD = predominately postural instability gait difficulty; p-TD = predominately tremor dominant; SMA = supplementary motor area.

Figure 2. Areas of gray matter atrophy derived from a direct comparison between patients with TD (n = 37) and PIGD subtypes (n = 60) using a ratio of symptoms to determine the group classification

The results are superimposed in representative sagittal and axial sections of a customized gray matter template, at a threshold of p < 0.05, cluster-level corrected. The results shown here are very similar to those shown in figure 1, supporting the idea that the results for the p-TD and p-PIGD comparisons are generalizable. IFG = inferior frontal gyrus; IPL = inferior parietal lobe; PHG = parahippocampal gyrus; p-PIGD = predominately postural instability gait difficulty; p-TD = predominately tremor dominant; SMA = supplementary motor area.