White-matter changes correlate with cognitive functioning in Parkinson's disease

Abstract

Diffusion tensor imaging (DTI) findings from emerging studies of cortical white-matter integrity in Parkinson's disease (PD) without dementia are inconclusive. When white-matter changes have been found, their relationship to cognitive functioning in PD has not been carefully investigated. To better characterize changes in tissue diffusivity and to understand their functional significance, the present study conducted DTI in 25 PD patients without dementia and 26 controls of similar ages. An automated tract-based DTI method was used. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were analyzed. Neuropsychological measures of executive functioning (working memory, verbal fluency, cognitive flexibility, inhibitory control) and visuospatial ability were then correlated with regions of interest that showed abnormal diffusivity in the PD group. We found widespread reductions in FA and increases in MD in the PD group relative to controls. These changes were predominantly related to an increase in RD. Increased AD in the PD group was limited to specific frontal tracks of the right hemisphere, possibly signifying more significant tissue changes. Motor symptom severity did not correlate with FA. However, different measures of executive functioning and visuospatial ability correlated with FA in different segments of tracts, which contain fiber pathways to cortical regions that are thought to support specific cognitive processes. The findings suggest that abnormal tissue diffusivity may be sensitive to subtle cognitive changes in PD, some of which may be prognostic of future cognitive decline.

Keywords: Parkinson’s disease; cerebral cortex; cognition; diffusion tensor imaging; white-matter.

Figure 1

White-matter diffusivity changes in Parkinson’s disease (PD). Axial and sagittal views of regions showing significantly lower fractional anisotropy (A) and higher mean diffusivity (B), axial diffusivity (C), and radial diffusivity (D) in the PD group relative to the control group (red clusters). The averaged FA-skeleton is displayed in green. Volumes of clusters showing significant change in PD were expanded on the figure to increase their visibility. White-matter tracts (E) showing significant diffusivity changes in PD were specified using the Johns Hopkins University (JHU) white-matter tractography atlas. Color labels for the JHU tracts are displayed at the bottom. Z coordinates (mm) of slices are from the Montreal Neurological Institute atlas. L, left hemisphere; R, right hemisphere.

Figure 2

Partial correlations between verbal working memory and fractional anisotropy (FA) in PD. Scatter plots show the relationship between Digit Span Forward and Digit Span Backward to FA in representative ROI. The values plotted for all measures are residuals from the regression of age and gender onto regional FA and cognitive performance. Cognitive measures were normalized to the control group by subtracting the individual raw scores for each measure from the control group mean and then dividing by the control group standard deviation. Higher Z scores reflect better performance. The spatial location of FA in each ROI is displayed in diffusion space for representative individual subjects. L, left hemisphere; CC, corpus callosum; RMF, rostral middle frontal; SCR, superior corona radiata. Coordinates designate distance in mm from anterior commissure: x, left (−)/right (+) and z, superior (+)/inferior (−).

Figure 3

Partial correlations between tests of executive and visuospatial functioning and fractional anisotropy (FA) in PD. Scatter plots show the relationship between verbal fluency, cognitive flexibility (Trails B-A), inhibition (Stroop Interference), and visuospatial (JOLT) functioning and FA in representative ROI. The values plotted for all measures are residuals from the regression of age and gender onto regional FA and cognitive performance. Cognitive measures were normalized to the control group by subtracting the individual raw scores for each measure from the control group mean and then dividing by the control group standard deviation. Higher Z scores reflect better performance, except for cognitive flexibility where higher values signify worse performance (i.e., longer time to complete Trails Part B after subtracting Part A performance). The spatial location of FA in each ROI is displayed in diffusion space for representative individual subjects. L, left hemisphere; R, right hemisphere; ARC, anterior corona radiata; cAC, caudal anterior cingulate; pOper, pars opercularis; pTriang, pars triangularis; RMF, rostral middle frontal. Coordinates designate distance in millimeters. from anterior commissure: x, left (−)/right (+); y, anterior (+)/posterior (−); and z, superior (+)/inferior (−).