Gray and white matter imaging: A biomarker for cognitive impairment in early Parkinson's disease?

Abstract

Background: The aim of this work was to investigate the cortical and white matter changes that underlie cognitive impairment in patients with incident Parkinson’s disease (PD) disease using voxel-based morphometry and diffusion tensor imaging. Methods: Newly diagnosed nondemented PD (n 5 125) and control subjects (n 5 50) were recruited from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson’s Disease Study and completed cognitive assessments and 3T structural and diffusion tensor MR imaging. Voxel-based morphometry was performed to investigate the relationship between gray matter volume and cognitive ability. Microstructural white matter changes were assessed with diffusion tensor imaging measures of fractional anisotropy and mean diffusivity using tract-based spatial statistics. Results: Increased mean diffusivity was observed bilaterally in subjects with PD, relative to controls (P 5 0.019). Increased mean diffusivity was associated with performance on the semantic fluency and Tower of London tasks in frontal and parietal white matter tracts, including the cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and inferior frontooccipital fasciculus. There was no difference in total gray matter volume between groups; however, bilateral reductions in frontal and parietal gray matter volume were associated with reduced performance on measures of executive function in PD subjects. Conclusions: At the earliest stages of PD, regionally specific increases in central white matter mean diffusivity are present and suggest early axonal damage. Such changes are not accompanied by significant gray matter volume loss and are consistent with proposed models of pathological progression of the disease. Structural MRI, especially diffusion tensor imaging analysis, offers potential as a noninvasive biomarker reflecting cognitive impairment in PD.