Longitudinal white matter microstructural change in Parkinson's disease

Postmortem studies of Parkinson's disease (PD) suggest that Lewy body pathology accumulates in a predictable topographical sequence, beginning in the olfactory bulb, followed by caudal brainstem, substantia nigra, limbic cortex, and neocortex. Diffusion-weighted imaging (DWI) is sensitive, if not specific, to early disease-related white matter (WM) change in a variety of traumatic and degenerative brain diseases. Although numerous cross-sectional studies have reported DWI differences in cerebral WM in PD, only a few longitudinal studies have investigated whether DWI change exceeds that of normal aging or coincides with regional Lewy body accumulation. This study mapped regional differences in the rate of DWI-based microstructural change between 29 PD patients and 43 age-matched controls over 18 months. Iterative within- and between-subject tensor-based registration was completed on motion- and eddy current-corrected DWI images, then baseline versus follow-up difference maps of fractional anisotropy, mean, radial, and axial diffusivity were analyzed in the Biological Parametric Mapping toolbox for MATLAB. This analysis showed that PD patients had a greater decline in WM integrity in the rostral brainstem, caudal subcortical WM, and cerebellar peduncles, compared with controls. In addition, patients with unilateral clinical signs at baseline experienced a greater rate of WM change over the 18-month study than patients with bilateral signs. These findings suggest that rate of WM microstructural change in PD exceeds that of normal aging and is maximal during early stage disease. In addition, the neuroanatomic locations (rostral brainstem and subcortical WM) of accelerated WM change fit with current theories of topographic disease progression.