White matter integrity and cognition in Parkinson's disease: a cross-sectional study

Abstract

Objective: We used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinson's disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimer's disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance.

Methods: This study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group.

Results: Patients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities.

Conclusions: In early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD.

Figure 1

An automated labelling system for subdividing the human cerebral cortex on MRI into gyral-based regions of interest (ROI), by Desikan et al. Presented are cortical representations of the six preplanned ROIs, here shown in one hemisphere. The left picture illustrates the lateral view of the hemisphere, the right showing the medial view of the hemisphere. Red=the middle frontal gyrus (rostral division), blue=the orbitofrontal cortex (medial division), yellow=lingual cortex, light green=parahippocampal cortex, dark green=entorhinal cortex, purple=precuneus.

Figure 2

Radial diffusivity in white matter underlying entorhinal cortex (ERC-WM) in Alzheimer's disease mild cognitive impairment (AD-MCI), Parkinson's disease (PD) and normal controls.

Figure 3

Radial diffusivity in white matter underlying the lingual gyrus (L-WM DR) in Alzheimer's disease mild cognitive impairment (AD-MCI), Parkinson's disease (PD) and normal controls.

Figure 4

Regions of increased radial diffusivity (DR; green) in patients with Alzheimer's disease as compared with control participants superimposed on the mean fractional anisotropy map from all participants (blue). Widespread differences in both hemispheres are seen. No voxels were significant for reduced DR. Multiple comparisons were corrected for by threshold-free cluster enhancement with the threshold set at p<0.05, and the significant voxels are inflated for ease of viewing. The statistical maps are shown as overlays on the Montreal Neurological Institutes template (annotated with the corresponding y-coordinates).

Figure 5

Regions of decreased fractional anisotropy (FA; red) in patients with Parkinson's disease compared with control participants superimposed on the mean FA map from all participants (blue). Significant changes are mainly seen in frontoparietal regions, corpus callosum and the posterior parts of cingulum. No voxels were significant for increased FA. Multiple comparisons were corrected for by threshold-free cluster enhancement with the threshold set at p<0.05, and the significant voxels are inflated for ease of viewing. The statistical maps are shown as overlays on the Montreal Neurological Institutes template (annotated with the corresponding y-coordinates).

Figure 6

Regions of increased radial diffusivity (DR; red) in patients with Parkinson's disease compared with Alzheimer's disease superimposed on the mean fractional anisotropy map from all participants (blue). Significant changes are seen mainly in frontoparietal regions on the left side including parts of the corticospinal tracts. No voxels were significant for reduced DR. Multiple comparisons were corrected for by threshold-free cluster enhancement with the threshold set at p<0.05, and the significant voxels are inflated for ease of viewing. The statistical maps are shown as overlays on the Montreal Neurological Institutes template (annotated with the corresponding y-coordinates). All significant changes shown reflect higher DR in Alzheimer's disease.

Figure 7

Significant voxel-wise correlations (red) between increased radial diffusivity (DR) and decreased total score on Rey Complex Figure Test in patients with Parkinson's disease superimposed on the mean fractional anisotropy map from all participants (blue). Significant correlations are mainly seen in posterior parts of corpus callosum. No voxels were significant for reduced DR. Multiple comparisons were corrected for by threshold-free cluster enhancement with the threshold set at p<0.05, and the significant voxels are inflated for ease of viewing. The statistical maps are shown as overlays on the Montreal Neurological Institutes template (annotated with the corresponding y-coordinates).